1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) disrupts social memory/recognition processes in the male mouse.
*Social Behavior; 1-Methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine/*analogs & derivatives/pharmacology; Animals; Brain Chemistry/drug effects; Catecholamines/metabolism; Cognition/*drug effects; Dopamine Agents/*pharmacology; Dopamine/metabolism; Habituation; Levodopa/pharmacology; Male; Memory/*drug effects; Mice; Psychophysiologic/drug effects
Male mice treated with MPTP or vehicle were tested for their ability to demonstrate a memory-recognition response as evaluated in a habituation-dishabituation task. Treatment with MPTP severely disrupted the male's habituation-dishabituation response profile compared to vehicle treated animals. Administration of L-DOPA at 45 min prior to behavioral testing in MPTP animals restored their performance on the habituation-dishabituation test to levels observed in vehicle treated animals. There was also a tendency for L-DOPA to produce enhanced responsiveness in vehicle treated animals. Mice treated with MPTP had significantly reduced concentrations of norepinephrine within the olfactory bulb and hippocampus. Vehicle treated mice administered L-DOPA had significantly increased dopamine concentrations within the corpus striatum. These results suggest that, in addition to its putative effects upon the nigrostriatal dopaminergic system and motor behavior, MPTP is also exerting substantial effects upon other systems. In particular, the noradrenergic system and its potential involvement with memory/recognition processes in the CD-1 mouse appears to be very sensitive to the neurotoxic effects of MPTP.
Dluzen D E; Kreutzberg J D
Brain research
1993
1993-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-8993(93)90860-p" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(93)90860-p</a>
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces norepinephrine concentrations in the olfactory bulbs of male mice.
*Sex Characteristics; 1-Methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine/*pharmacology; Animals; Dopamine/metabolism; Drug Resistance/genetics; Inbred C57BL; Inbred Strains; Male; Mice; Norepinephrine/*metabolism; Olfactory Bulb/*metabolism; Osmolar Concentration
Male retired breeder C57/Bl and CD-1 mice were treated with either MPTP or its vehicle. At 7-10 days post-treatment, catecholamine concentrations within the olfactory bulbs (OB) and hypothalamus were determined. Norepinephrine concentrations within the OB were significantly decreased in MPTP-treated mice. These effects were more pronounced in the CD-1 (50% reduction) compared to the C57/Bl (20% reduction) strain. No effects of MPTP were observed on norepinephrine concentrations within the hypothalamus. Dopamine concentrations in the OB and hypothalamus did not differ between MPTP- and vehicle-treated mice in either strain. Overall, catecholamine concentrations within the OB, but not the hypothalamus, were significantly greater in C57/Bl compared to CD-1 mice. The reduction in OB norepinephrine concentration in the MPTP-treated animals may be related to the olfactory deficits which accompany Parkinson's disease.
Dluzen D E
Brain research
1992
1992-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-8993(92)91385-r" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(92)91385-r</a>
Ablation of the hypothalamic arcuate-median eminence region reduces the concentration of vasoactive intestinal peptide in the anterior pituitary gland of male rats.
Adrenal Glands/anatomy & histology; Animals; Anterior/*physiology; Arcuate Nucleus of Hypothalamus/*physiology; Drinking Behavior; Hypothalamo-Hypophyseal System/*physiology; Male; Median Eminence/*physiology; Organ Size; Pituitary Gland; Pituitary Gland/anatomy & histology; Prolactin/blood/metabolism; Rats; Sprague-Dawley; Testis/anatomy & histology; Time Factors; Vasoactive Intestinal Peptide/*metabolism
This study was designed to determine the influence of the hypothalamus on the content of vasoactive intestinal peptide (VIP) in the anterior pituitary. Disruption of the hypothalamic-pituitary connection was performed by ablating the arcuate-median eminence (ARC-ME) region in adult male rats. Fifteen days later, there was a significant reduction in pituitary mass, adrenal and testicular weight and an increase in water consumption and serum prolactin levels indicating the elimination of hypothalamic influence on the pituitary gland in the ARC-ME group when compared to controls. Anterior pituitary VIP content was also significantly reduced in the lesion group. These data suggest that the hypothalamus is involved in the regulation of pituitary VIP.
Carrillo A J; Dluzen D E
Brain research
1993
1993-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-8993(93)90910-f" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(93)90910-f</a>
Acute effects of estrogen upon methamphetamine induced neurotoxicity of the nigrostriatal dopaminergic system.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Animals; Dopamine/metabolism; Drug Interactions; Estrogens/metabolism/*pharmacology; Female; Methamphetamine/antagonists & inhibitors/*toxicity; Mice; Neostriatum/*drug effects/metabolism/physiopathology; Neural Pathways/*drug effects/metabolism/physiopathology; Neuroprotective Agents/metabolism/pharmacology; Neurotoxins/antagonists & inhibitors/toxicity; Ovariectomy; Parkinson Disease/drug therapy/metabolism/physiopathology; Presynaptic Terminals/drug effects/metabolism; Reaction Time/drug effects/physiology; Sex Factors; Substantia Nigra/*drug effects/metabolism/physiopathology
Estrogen acts as a neuroprotectant of the nigrostriatal dopaminergic system when given chronically to female mice prior to Methamphetamine (MA) insult. In this report, we tested the acute effects of Estradiol Benzoate (EB-10 microg in Oil) in ovariectomized CD-1 mice to function as a neuroprotectant when administered prior to (Experiment 1) or after (Experiment 2) MA treatment. Striatal dopamine (DA) concentrations and DOPAC/DA ratios were measured to assess the neuroprotective effects of EB. In Experiment 1, we observed that EB exerted a neuroprotective effect upon striatal dopamine concentrations when administered at 24 and 12, but not at 0.5, hours prior to MA injection and upon DOPAC/DA ratios when administered at 24, 12 and 0.5 hours prior to MA. In Experiment 2, no evidence for estrogen to protect the striatum from MA insult was obtained when EB was administered at 15, 30, 60 or 120 minutes after MA. These results show that EB can act as a modulator of MA-induced nigrostriatal dopaminergic neurotoxicity suggestive of a neuroprotectant, when administered within 0.5 hour of MA insult as assessed by measures of DOPAC/DA, but fails to prevent depletion of DA when given after MA insult. The data suggest that estrogen may exert this rapid neuroprotective effect through a non-genomic mechanism.
Gajjar T M; Anderson L I; Dluzen D E
Journal of neural transmission (Vienna, Austria : 1996)
2003
2003-11
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s00702-003-0045-3" target="_blank" rel="noreferrer noopener">10.1007/s00702-003-0045-3</a>
Age related changes of social memory/recognition in male Fischer 344 rats.
*Social Behavior; Aging/*physiology; Animal/physiology; Animals; Arousal/physiology; Female; Habituation; Inbred F344; Male; Mental Recall/*physiology; Psychophysiologic/*physiology; Psychophysiology; Rats; Retention (Psychology)/physiology; Sexual Behavior; Social Environment
Two different habituation-dishabituation test paradigms were used to evaluate differences in social memory/recognition among 3-, 15- and 22-month-old male Fischer 344 rats. For test 1, males received three 2-min exposures to the same stimulus ovariectomized female, followed by three 2-min exposures to a different stimulus female with an inter-trial interval of 6 min. All groups showed a habituation response with investigation times decreasing on trials 2 and 3. Introduction of a different stimulus female on trial 4 (dishabituation) resulted in significant differences with investigation times of the 3-month animals being significantly greater than both the 15- and 22-month animals and those of the 15- being greater than the 22-month animals. Notably, the 22-month-old animals failed to dishabituate on this task. For test 2, all animals received two trials with different stimulus females used in each trial. While investigation times of the
Guan X; Dluzen D E
Behavioural brain research
1994
1994-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0166-4328(94)90011-6" target="_blank" rel="noreferrer noopener">10.1016/0166-4328(94)90011-6</a>
AGE-DEPENDENT CHANGES IN OLFACTORY-MEDIATED BEHAVIORAL INVESTIGATIONS IN THE MALE-RAT
Psychology; responses; Neurosciences & Neurology; parkinsons-disease; Behavioral Sciences; recognition; alzheimers-disease; identification; norepinephrine; deficits; bulb; mitral cells; sex odors
Menciowszalek T; Ramirez V D; Dluzen D E
Behavioral and Neural Biology
1992
1992-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0163-1047(92)90164-y" target="_blank" rel="noreferrer noopener">10.1016/0163-1047(92)90164-y</a>
Age-related changes in monoamines within the olfactory bulbs of the Fischer 344 male rat.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Aging/*metabolism; Animals; Biogenic Monoamines/*metabolism; Dopamine/metabolism; Inbred F344; Male; Olfactory Bulb/*metabolism; Rats; Serotonin/metabolism
In this report the olfactory bulbs (OB) were removed from 5-6 month, 15-16 month and 25-26 month male Fischer 344 rats and assayed for concentrations of monoamines and their metabolites using HPLC-EC. Concentrations of norepinephrine were significantly greater in 25-26 and 15-16 compared to the 5-6 month old rats. By contrast, the norepinephrine metabolite, 3-methoxy-4-hydroxyphenyl glycol (MHPG), was significantly lower in the 25-26 vs. the 15-16 and 5-6 month old animals. While OB concentrations of dopamine and serotonin did not differ among the three age groups, their respective metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole-3-acetic acid (5-HIAA), were significantly reduced in the 15-16 and 25-26 month old animals compared to the 5-6 month old animals. These data show some of the age related changes which occur in the monoamines of the OB of the Fischer 344 rat. The salient bi-directional changes which are observed between norepinephrine and its metabolite, MHPG, are particularly intriguing since they reveal some of the mechanistic alterations that occur in the OB noradrenergic system, which may underlie the age related changes in olfactory related memory/recognition processes.
Dluzen D E
Mechanisms of ageing and development
1996
1996-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0047-6374(96)01774-5" target="_blank" rel="noreferrer noopener">10.1016/0047-6374(96)01774-5</a>
Age-related changes in nigrostriatal dopaminergic function are accentuated in +/- brain-derived neurotrophic factor mice.
*Aging; Animals; Brain-Derived Neurotrophic Factor/*genetics/*metabolism; Corpus Striatum/*metabolism; Dopamine/*biosynthesis; Mice; Motor Activity/physiology; Mutant Strains; Mutation; Substantia Nigra/*metabolism
The effects of a deletion for the brain derived neurotrophic factor (BDNF) allele (+/- BDNF) upon age-related changes in nigrostriatal dopaminergic (NSDA) function were assessed. Behavioral (beam crossing and spontaneous activity) and neurochemical (potassium-stimulated dopamine release from superfused striatum) measures were compared among Young (4-5 month), Middle (11-13 month) and Aged (19-21 month) +/- BDNF and their wild type littermate control (+/+ BDNF) mice. No statistically significant differences were obtained between +/+ and +/- BDNF mice at the Young age sampling period for any of the behavioral or neurochemical measures. Behavioral and neurochemical responses indices of NSDA function begin to diverge between +/+ and +/- Middle age BDNF mice and maximal differences were observed at the Aged period. For both movement and stereotypy times, scores obtained from +/+ mice were significantly decreased compared with +/- BDNF mice at the Aged period and center time scores of +/+ mice were decreased at both the Middle and Aged periods compared with +/- BDNF mice. Neurochemically, potassium-stimulated DA release of +/+ mice was significantly greater than +/- BDNF mice with maximal differences obtained at the Aged period. These results demonstrate marked differences in age-related changes of NSDA function between +/+ and +/- BDNF mice and suggest that the deletion of one allele for BDNF may make these mice more susceptible to age-related declines in NSDA function.
Dluzen D E; McDermott J L; Anderson L I; Kucera J; Joyce J N; Osredkar T; Walro J M
Neuroscience
2004
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2004.06.032" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2004.06.032</a>
Age-related size reduction of foramina in the cribriform plate.
80 and over; Adult; Age Distribution; Aged; Aging/*physiology; Analysis of Variance; Ethmoid Bone/*anatomy & histology; Female; Humans; Male; Middle Aged; Olfactory Nerve/anatomy & histology; Sex Distribution; Smell/physiology
Anecdotal evidence suggests that the foramina of the cribriform plate which transmit cranial nerve I decrease in size with age, but this finding has never been supported with quantitative data. It has also been observed that olfactory function declines with increasing age. It has been hypothesized that the cribriform plate foramina closure may be responsible for the olfactory performance decrease with age. We gathered quantitative data to test an age-related decline in cribriform plate foramina area. We report data for the area of patent foramina in the posterior 1 cm of 57 cribriform plates from 40 skulls of known age and sex. Analyses were performed to test for the effects of age, sex, and lateralization on foramina area. The area of patent foramina in the cribriform plate decreases with increasing age. Age is a strong covariate with foramina area (P value = 0.0025). The regression equation for the area of patent foramina is: expected area = 8.17 - (0.06) age. Adding the variable sex does not contribute significantly (P value \textgreater 0.28) to the model which utilizes age alone. Nor was there any significant lateralization in patent foramina area. The area of patent foramina in the cribriform plate decreases with increasing age, and there is no significant difference between males and females or left and right sides. Such decreases in patent foramina may be associated with impaired olfactory function in the aged.
Kalmey J K; Thewissen J G; Dluzen D E
The Anatomical record
1998
1998-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/(sici)1097-0185(199807)251:3%3C326::aid-ar7%3E3.0.co;2-t" target="_blank" rel="noreferrer noopener">10.1002/(sici)1097-0185(199807)251:3%3C326::aid-ar7%3E3.0.co;2-t</a>
Aging and sex differences in striatal dopaminergic function.
3; 4-Dihydroxyphenylacetic Acid/metabolism; Aging/*physiology; Amphetamine/pharmacology; Animals; Chemical; Dopamine Uptake Inhibitors/pharmacology; Dopamine/metabolism/*physiology; Female; In Vitro Techniques; Male; Mice; Neostriatum/metabolism/*physiology; Organ Size/physiology; Potassium/pharmacology; Sex Characteristics; Stimulation; Uterus/physiology
In this report the potassium- (30 mM) and amphetamine- (10 microM) stimulated responses of dopamine (DA) and 3,4-dihydroxy phenylacetic acid (DOPAC) from superfused striatal tissue of female and male mice as sampled at 2, 6, 18 and 24 months of age were compared. When assessed relative to responses obtained from
McDermott J L; Dluzen D E
Neuroscience
2007
2007-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2007.06.058" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2007.06.058</a>
Alteration in L-DOPA evoked dopamine and DOPAC output under conditions of impaired vesicular dopamine storage.
3; 4-Dihydroxyphenylacetic Acid/*metabolism; Animals; Dopamine Agents/*pharmacology; Dopamine/*metabolism; Levodopa/*pharmacology; Male; Pharmaceutical Vehicles; Rats; Reserpine/pharmacology; Sprague-Dawley; Synaptic Vesicles/*drug effects/metabolism; Tetrabenazine/pharmacology
We examined the effect of L-dihydroxyphenylalanine (L-DOPA) infusion in vitro upon dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) output from superfused corpus striatum of vehicle and reserpine or tetrabenazine (TBZ) treated male rats. Specifically, we tested the effects of two 20-min infusions of L-DOPA (5 uM) upon DA and DOPAC output (pg/mg/min) in reserpine (5 mg/kg, i.p., 24 hours before sacrifice; n=11), TBZ (30 mg/kg, i.p. 1 hour before sacrifice; n=8) or vehicle (n=21) treated rats. There was an overall significantly higher L-DOPA evoked DA output from the vehicle (12.22+/-1.74) versus reserpine (4.39+/-2.40) (p \textless 0.05), but not TBZ (9.16+/-2.81) treated rats. In addition, the DA response to the second L-DOPA infusion was significantly increased over that of the first response in the vehicle (9.40+/-2.11 vs. 15.04+/-2.78) (p \textless 0.05), but not reserpine or TBZ treated rats. The overall DOPAC outputs did not achieve a statistically significant difference among all treatment groups. However, the DOPAC outputs following the second L-DOPA infusion were significantly reduced in reserpine (41.15+/-6.10 vs. 20.27+/-4.54) and TBZ (21.38+/-4.41 vs. 10.87+/-2.36) (both p \textless 0.05), but not vehicle (28.99+/-4.00 vs. 24.91+/-4.78) treated rats. We conclude that: 1) the storage capacity of DA neurons is one of the important elements involved in affecting L-DOPA's effects upon DA and DOPAC output, 2) the shunting of storage to metabolism may represent a common characteristic in impaired nigrostriatal dopaminergic system, and 3) TBZ may operate differently from reserpine in the nigrostriatal dopaminergic system.
Xu K; Dluzen D E
Journal of neural transmission (Vienna, Austria : 1996)
1998
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1007/s007020050114" target="_blank" rel="noreferrer noopener">10.1007/s007020050114</a>
Alteration of dopamine release by rat caudate putamen tissues superfused with alpha 2-macroglobulin.
alpha-Macroglobulins/drug effects/*pharmacology/physiology; Alzheimer Disease/metabolism; Animals; Caudate Nucleus/*drug effects/metabolism; Chemical; Dopamine/*metabolism; Male; Methylamines/pharmacology; Nerve Growth Factor/physiology; Nerve Growth Factors/physiology; Neurotoxins/*pharmacology; Parkinson Disease/metabolism; Perfusion; Putamen/*drug effects/metabolism; Rats; Receptors; Sprague-Dawley; Stimulation
Monoamine-activated alpha-2-macroglobulin (alpha 2M) has been shown to decrease the dopamine concentrations in rat caudate putamen (CP) in vivo as well as inhibit choline acetyltransferase activities in the culture of basal forebrain neurons. In this study, we further investigated the effects of methylamine-activated alpha 2M (MA-alpha 2M) upon striatal dopaminergic function by determining whether a direct infusion of this glycoprotein will alter dopamine (DA) release in vitro from superfused CP tissue fragments. In experiment 1, an infusion of 2.8 microM MA-alpha 2M produced a statistically significant increase in DA release compared with control superfusions. In experiment 2, varying doses (0, 0.7, 1.4, 2.8, 4.1 microM) of MA-alpha 2M were tested for their capacity to alter DA release. Only the 2.8 microM dose of MA-alpha 2M was effective in producing a significant increase of DA release. In experiment 3, the normal form of alpha 2M (N-alpha 2M) at 2.8 microM was compared with the control superfusions. The infusion of N-alpha 2M produced an increase in DA release which was substantially lower than the DA increase induced by MA-alpha 2M, and not significantly different from that of the control superfusion. These results show that MA-alpha 2M, like some other neurotoxins, can markedly alter CP dopaminergic function as indicated by the acute increase in DA release following infusion of this glycoprotein, and these effects are exerted at a relatively narrow range of doses. Taken together, these data suggest that this glycoprotein, if allowed to accumulate in the central nervous system (CNS), may promote some neurodegenerative changes that can occur in disorders like Parkinson's disease.
Hu Y Q; Liu B J; Dluzen D E; Koo P H
Journal of neuroscience research
1996
1996-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jnr.490430109" target="_blank" rel="noreferrer noopener">10.1002/jnr.490430109</a>
Alterations in nigrostriatal dopaminergic function within BDNF mutant mice.
Animals; Brain-Derived Neurotrophic Factor/deficiency/genetics/*physiology; Corpus Striatum/*metabolism; Dopamine/*metabolism; Heterozygote; Hypothalamus/*metabolism; Knockout; Mice; Norepinephrine/metabolism; Olfactory Bulb/metabolism; Polymerase Chain Reaction; Reference Values; Substantia Nigra/*metabolism
The influence of brain-derived neurotrophic factor (BDNF) upon the nigrostriatal dopaminergic system was evaluated in weanling and adult mice carrying a targeted inactivated BDNF gene. Regional specificity of this BDNF mutation was assessed by assaying catecholamine concentrations within the corpus striatum, hypothalamus, and olfactory bulbs. In weanling mice dopamine, but not norepinephrine, concentrations within the corpus striatum of homozygous mutant (-/-) mice were significantly reduced with levels being 54% that of the wild-type controls (+/+) and 49% that of the heterozygous mutant (+/-) mice. While no differences were obtained among the three genotypes for hypothalamic dopamine, norepinephrine concentrations of -/- mice were significantly lower, being 62% of +/+ mice and 49% of +/- mice. The dopamine concentrations of -/- mice within the olfactory bulb were significantly reduced (69%) compared to the +/-, but not +/+ mice. Olfactory bulb norepinephrine concentrations showed a statistically significant difference among each of the three conditions with minimal levels in -/- mice (62% of +/+ and 45% of +/-). In the adults, catecholamine concentrations were measured only in +/+ and +/- mice since -/- mice do not typically survive past 21 days. Dopamine, but not norepinephrine, concentrations within the corpus striatum were significantly increased (116%) in +/- compared to +/+ mice. No other statistically significant differences were obtained in catecholamine concentrations within the hypothalamus or olfactory bulb in these adult mice. These results show that homozygous BDNF mutations produce severe depletions within the nigrostriatal dopaminergic system and substantial reductions of norepinephrine within the hypothalamus and olfactory bulb. Interestingly, maximal catecholamine concentrations for all areas sampled at both ages were observed in the +/- mice. These latter findings may indicate some subtle changes in catecholamine functions resulting from a heterozygous BDNF mutation.
Dluzen D E; Story G M; Xu K; Kucera J; Walro J M
Experimental neurology
1999
1999-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/exnr.1999.7225" target="_blank" rel="noreferrer noopener">10.1006/exnr.1999.7225</a>
Castration differentially alters [3H]nisoxetine binding to norepinephrine uptake sites in olfactory bulb and frontal cortex of male rats.
*Orchiectomy; Adrenergic/drug effects/*metabolism; Animals; Fluoxetine/*analogs & derivatives/metabolism; Frontal Lobe/drug effects/*metabolism; Kinetics; Male; Norepinephrine/metabolism; Olfactory Bulb/drug effects/*metabolism; Rats; Receptors; Sprague-Dawley; Synaptosomes/drug effects/metabolism; Testosterone/pharmacology
In the present study, [3H]nisoxetine binding to norepinephrine (NE) uptake sites and [3H]norepinephrine uptake were investigated within olfactory bulb (OB) and frontal cortex homogenates from intact and castrated male rats. Statistically significant reductions in the number of [3H]nisoxetine binding sites (Bmax) were found in OB from the castrates, while significantly increased Bmax values were obtained in the frontal cortex. Castration also significantly altered the affinity (Kd) of [3H]nisoxetine binding in the frontal cortex, but not in the OB. Assessment of [3H]norepinephrine uptake showed that in neither brain regions were there any statistically significant differences in Km nor Vmax between the castrated and intact male rats, indicating that the basal uptake process is not changed following castration in either of these brain areas. These results demonstrate the differential effects of castration upon [3H]nisoxetine binding sites between the OB and frontal cortex. Such findings provide new evidence for one of the mechanisms by which androgens may modulate central noradrenergic activity.
Shang Y; Boja J W; Dluzen D E
Synapse (New York, N.Y.)
1999
1999-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/(SICI)1098-2396(19990315)31:4%3C250::AID-SYN2%3E3.0.CO;2-Z" target="_blank" rel="noreferrer noopener">10.1002/(SICI)1098-2396(19990315)31:4%3C250::AID-SYN2%3E3.0.CO;2-Z</a>
Castration differentially alters H-3 nisoxetine binding to norepinephrine uptake sites in olfactory bulb and frontal cortex of male rats
androgens; cerebral-cortex; chemical cues; conspecific odors; depression; dopamine; h-3 nisoxetine; hormone-releasing hormone; induced plasticity; locus-coeruleus; memory/recognition; Neurosciences & Neurology; norepinephrine transporter; olfaction; transporter; transporter messenger-rna; tyrosine-hydroxylase
In the present study, [H-3]nisoxetine binding to norepinephrine (NE) uptake sites and [H-3]norepinephrine uptake were investigated within olfactory bulb (OB) and frontal cortex homogenates from intact and castrated male rats. Statistically significant reductions in the number of [H-3] nisoxetine binding sites (B-max) were found in OB from the castrates, while significantly increased B-max values were obtained in the frontal cortex. Castration also significantly altered the affinity (K-d) of [H-3]nisoxetine binding in the frontal cortex, but not in the OB. Assessment of [H-3]norepinephrine uptake showed that in neither brain regions were there any statistically significant differences in K-m nor V-max between the castrated and intact male rats, indicating that the basal uptake process is not changed following castration in either of these brain areas. These results demonstrate the differential effects of castration upon [H-3]nisoxetine binding sites between the OB and frontal cortex. Such findings provide new evidence for one of the mechanisms by which androgens may modulate central noradrenergic activity. Synapse 31:250-255, 1999. (C) 1999 Wiley-Liss, Inc.
Shang Y L; Boja J W; Dluzen D E
Synapse
1999
1999-03
Journal Article
<a href="http://doi.org/10.1002/(sici)1098-2396(19990315)31:4%3C250::aid-syn2%3E3.3.co;2-q" target="_blank" rel="noreferrer noopener">10.1002/(sici)1098-2396(19990315)31:4%3C250::aid-syn2%3E3.3.co;2-q</a>
Castration reduces olfactory bulb norepinephrine transporter function as indicated by responses to noradrenergic uptake blockers.
*Symporters; Adrenergic Uptake Inhibitors/*pharmacology; Animals; Atomoxetine Hydrochloride; Carrier Proteins/*metabolism; Infusions; Isotonic Solutions; Male; Norepinephrine Plasma Membrane Transport Proteins; Norepinephrine/*metabolism; Olfactory Bulb/*metabolism; Orchiectomy; Parenteral; Propylamines/pharmacology; Rats; Sprague-Dawley; Testis/*physiology; Thiophenes/pharmacology
It has been demonstrated that castration alters the functioning of the olfactory bulb (OB)-norepinephrine (NE) system. In the present experiment, we examined one of the mechanisms by which castration modulates the OB-NE system by comparing NE uptake activity between intact and castrated male rats as studied using an in vitro superfusion technique. To accomplish this goal, NE output from the OB of intact and castrated male rats in response to infusion with two different drugs which alter NE uptake functions, tomoxetine and talsupram, were tested. Overall, NE outputs in response to tomoxetine were significantly higher in the castrated than in intact rats and both groups were significantly greater than non-infused controls. For the talsupram infusion group, NE outputs from the castrated, but not intact rats, were significantly greater than controls. No statistically significant differences were detected between the castrated and intact rats. These results demonstrate that castration alters the NE uptake activities in response to these noradrenergic uptake blockers and suggest that one mechanism by which castration alters OB-NE functioning is through reducing the uptake activity of NE within the OB. Such findings have important implications for olfactory-based learning and memory/recognition processes which are believed to involve the OB-NE system and are altered following castration.
Shang Y; Dluzen D E
Brain research
1998
1998-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(97)01101-3" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(97)01101-3</a>
Daily spontaneous running alters behavioral and neurochemical indexes of nigrostriatal function.
Animal/*physiology; Animals; Behavior; Chromatography; Circadian Rhythm; Corpus Striatum/cytology/*physiology; Dopamine/*metabolism; High Pressure Liquid; In Vitro Techniques; Male; Neuropsychological Tests; Organ Size; Perfusion; Physical Conditioning; Potassium/*metabolism; Psychomotor Performance/*physiology; Random Allocation; Rats; Sprague-Dawley
Behavioral and neurochemical indexes of nigrostriatal dopaminergic function were compared between sedentary control rats (n = 12) and daily spontaneous running (DSR) male rats (n = 10). Nine weeks of DSR did not significantly alter body, heart, pituitary, or testes weights. DSR and control animals did differ in performance on a sensorimotor beam walking task, with DSR rats showing significantly shorter times required to cross the beam (60 +/- 17 vs. 119 +/- 14s; P \textless 0.02) as well as fewer slips off the beam (3.0 +/- 0.8 vs 6.2 +/- 1.1; P \textless 0.05). DSR animals also engaged in significantly greater durations of social investigation than control rats (43 +/- 5 vs 25 +/- 3 s; P \textless 0.01) when tested in a social investigation memory-recognition test. Basal dopamine release rates from superfused corpus striatal tissue fragments of DSR rats were about one-half those obtained from control animals (18 +/- 5 vs. 34 +/- 6 pg.mg-1.min-1; P \textless 0.05), whereas responses of these striatal tissue fragments to a depolarizing concentration of potassium were virtually identical (45 +/- 10 vs. 47 +/- 8 pg.mg-1.min-1). These data indicate that a relatively limited intensity of DSR insufficient to alter cardiovascular function can exert substantial effects on behavioral and neurochemical indicators of nigrostriatal dopaminergic activity.
Dluzen D E; Liu B; Chen C Y; DiCarlo S E
Journal of applied physiology (Bethesda, Md. : 1985)
1995
1995-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jappl.1995.78.4.1219" target="_blank" rel="noreferrer noopener">10.1152/jappl.1995.78.4.1219</a>
Decreased postnatal cardiac norepinephrine levels in NT3-deficient transgenic mice
Cell Biology
Story G M; Dluzen D E; DiCarlo S E; Walro J M
Molecular Biology of the Cell
1998
1998-11
Journal Article
n/a
Developmental And Genetic Influences Upon Gender Differences In Methamphetamine-induced Nigrostriatal Dopaminergic Neurotoxicity
bdnf mutant mice; brain; brain-derived neurotrophic factor (BDNF); differentiation; dopamine; estrogen; female mice; gonadal-hormones; messenger-rna; mptp-induced neurotoxicity; neurodegeneration; neuroprotection; neurotrophic factor; parkinsons-disease; sexual; sexual differences; testosterone; ventral mesencephalon
Dluzen D E; McDermott J L
Current Status of Drug Dependence / Abuse Studies: Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity
2004
2004
Book Chapter
n/a
Differences in reserpine-induced striatal dopamine output and content between female and male mice: implications for sex differences in vesicular monoamine transporter 2 function.
*Sex Characteristics; Adrenergic Uptake Inhibitors/*pharmacology; Animals; Chromatography; Corpus Striatum/drug effects/*metabolism; Dopamine/*metabolism; Female; High Pressure Liquid; Male; Mice; Orchiectomy; Ovariectomy; Reserpine/*pharmacology; Vesicular Monoamine Transport Proteins/*metabolism
In this report a series of six in vitro experiments in which reserpine-evoked dopamine output and two in vivo experiments in which the effects of reserpine injections upon dopamine content from striatal tissue of female and male mice were performed as a means to assess possible sex differences in vesicular monoamine transporter 2 (VMAT2) function. Significantly greater amounts of dopamine were obtained from striatal tissue of female mice in response to either a brief (experiment 1) or continuous (experiment 2) infusion of reserpine. Similarly, reserpine-evoked dopamine output from striatal tissue of gonadectomized females was significantly greater that that of gonadectomized males (experiment 3). When reserpine-evoked dopamine responses were compared directly between intact versus gonadectomized females (experiment 4) or males (experiment 5) no statistically significant differences were obtained. Finally, comparisons of gonadectomized females treated or not with estrogen revealed no statistically significant differences in reserpine-evoked dopamine output (experiment 6). Injections of reserpine produced significantly greater depletions of striatal dopamine content within intact female versus male mice (experiment 7). Dopamine contents of gonadectomized females treated or not with estrogen did not differ following treatment with reserpine, but were significantly greater than that of gonadectomized males (experiment 8). Taken together, these results show that female striatal tissue is more responsive to reserpine-evoked dopamine output, and this sex difference appears to be estrogen independent. Similarly, the dopamine depleting effects of reserpine are greater in intact female mice, however, gonadectomy reverses this effect in an estrogen independent manner. The data suggest that female mice may have a greater amount/activity of VMAT2 function as revealed by the increased responsiveness to the VMAT2 blocking drug, reserpine. Such differences in VMAT2 function may be related to the gender differences observed in conditions like Parkinson's disease and drug addiction.
Dluzen D E; Bhatt S; McDermott J L
Neuroscience
2008
2008-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2008.04.051" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2008.04.051</a>
Dopamine Transporter As A Marker Of Neuroprotection In Methamphetamine-lesioned Mice Treated Acutely With Estradiol
17-beta-estradiol; brain; depletion; dopamine transporter; Endocrinology & Metabolism; estrogen; gender-differences; gonadal steroids; induced neurotoxicity; methamphetamine; neuroprotection; Neurosciences & Neurology; parkinsons-disease; progesterone; rat; striatal dopamine; striatum; substantia nigra; system
D'Astous M; Gajjar T M; Dluzen D E; Di Paolo T
Neuroendocrinology
2004
1905-06
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1159/000079664" target="_blank" rel="noreferrer noopener">10.1159/000079664</a>
Effect Of Alpha-2-macroglobulin (alpha(2)m) Versus Alpha(1)m On Monoamine-neurotransmitter Systems, Axonal Growth And The Survival Of Cerebral Neurons
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Liebl D J; Hu Y O; Dluzen D E; Koo P H
Faseb Journal
1994
1994-04
Journal Article or Conference Abstract Publication
n/a
EFFECTS OF ESTROGEN-TREATMENT ON SENSORIMOTOR TASK-PERFORMANCE AND BRAIN DOPAMINE CONCENTRATIONS IN GONADECTOMIZED MALE AND FEMALE CD-1 MICE
Endocrinology & Metabolism; parkinsons-disease; Behavioral Sciences; Sensitivity; striatum; amphetamine; sex-differences; estradiol; release; locomotor-activity; castrated male-rats; rotational behavior
In Experiment I, castrated male and female CD-1 mice +/- estradiol benzoate (EB) treatment were tested for their performance on a skilled sensorimotor task consisting of walking across beams of varying widths (6, 9, 12, and 21 mm). To evaluate whether behavioral performance was related to nigrostriatal dopaminergic function, tissue dopamine concentrations were determined from the corpus striatum as well as the hypothalamus and olfactory tubercle. In general, sensorimotor performance improved for all treatment conditions as the beam width increased. Castrated male mice treated with oil vehicle showed the worst performance as indicated by significantly greater amounts of time to cross the beam. Treatment of castrated males with EB significantly improved their performance. Performance of the castrated females was not changed by EB treatment and was similar to that observed with the castrated + EB males. Significant gender differences in dopamine concentrations (female > male) were obtained in the corpus striatum, as well as the olfactory tubercle and hypothalamus. Dopamine levels were unaltered by EB treatment. In Experiment II, behavioral and neurochemical determinations were directly compared between castrated and intact male mice. Behavioral performance of castrates was significantly reduced compared to intact males. No differences in dopamine concentrations were obtained between these two groups; however, the hypothalamic dopamine/DOPAC ratio of castrates was significantly greater than that of intact male mice. These results demonstrate significant modulatory effects of EB in castrated male, but not female, mice upon sensorimotor performance and indicate that this task may provide an effective means to partial out modulatory effects of gonadal steroid hormones upon skilled sensorimotor performance. When the data of Experiments I and II are combined, it appears that the basis of this sensorimotor deficit in the males is the absence of gonadal steroid hormones. In addition, these results reveal significant gender differences in various dopaminergic systems in these mice. (C) 1994 Academic Press, Inc.
McDermott J L; Kreutzberg J D; Liu B J; Dluzen D E
Hormones and Behavior
1994
1994-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1006/hbeh.1994.1002" target="_blank" rel="noreferrer noopener">10.1006/hbeh.1994.1002</a>
Effects of neonatal and prepubertal hormonal manipulations upon estrogen neuroprotection of the nigrostriatal dopaminergic system within female and male mice.
*Sex Characteristics; Aging/metabolism; Animal; Animals; Disease Models; Dopamine/metabolism; Estrogens/metabolism/*pharmacology; Female; Gonads/growth & development/metabolism; Male; Methamphetamine/antagonists & inhibitors/toxicity; Mice; Neostriatum/*drug effects/metabolism/physiopathology; Neural Pathways/drug effects/metabolism/physiopathology; Neuroprotective Agents/metabolism/*pharmacology; Newborn; Orchiectomy; Ovariectomy; Sexual Maturation/physiology; Substantia Nigra/*drug effects/metabolism/physiopathology; Testosterone/metabolism/*pharmacology
Estrogen (E) can function as a neuroprotectant of the nigrostriatal dopaminergic (NSDA) system against methamphetamine (MA) neurotoxicity in female, but not male, mice. In the present report we examined whether the organizational effects of gonadal steroid hormones, as exerted in the early postnatal period, or developmental effects, as exerted during the pubertal period, would contribute to this sexually dimorphic neuroprotectant action of E. Neonatal gonadectomy and treatment with testosterone of female mice, retained the ability to show an E neuroprotectant response when tested as adults. However, females not treated with gonadal steroids failed to show an E-dependent neuroprotectant response. Neonatal gonadectomy of male mice, failed to result in the display of an E neuroprotectant response when tested as adults. Prepubertal gonadectomy of female mice, with or without testosterone treatment, abolished the capacity for E to produce neuroprotection against MA-induced NSDA neurotoxicity. Nor did prepubertal gonadectomy enable male mice to show an E neuroprotectant response. Taken together these results demonstrate that none of the manipulations performed within male mice enabled them to show an E-dependent neuroprotective response against MA-induced neurotoxicity of the NSDA system when tested as adults. For the female, it appears that the presences of gonadal steroids at these two developmental periods are needed for the display of an E-dependent neuroprotectant response within the adult.
Anderson L I; Leipheimer R E; Dluzen D E
Neuroscience
2005
1905-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/j.neuroscience.2004.09.033" target="_blank" rel="noreferrer noopener">10.1016/j.neuroscience.2004.09.033</a>
Effects of testosterone upon MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system of C57/B1 mice.
*MPTP Poisoning; 1-Methyl-4-phenyl-1; 2; 3; 4-Dihydroxyphenylacetic Acid/metabolism; 6-tetrahydropyridine/*antagonists & inhibitors; Animals; Catecholamines/metabolism; Dopamine Agents/*toxicity; Dopamine/metabolism/*physiology; Female; Inbred C57BL; Male; Mice; Neostriatum/drug effects/metabolism/*pathology; Nervous System Diseases/chemically induced/*pathology/*prevention & control; Olfactory Bulb/drug effects/metabolism; Orchiectomy; Substantia Nigra/drug effects/metabolism/*pathology; Testosterone/*pharmacology
We have recently reported that treatment of gonadectomized female and male C57/B1 mice with the gonadal steroid hormone, estrogen, reduced nigrostriatal dopaminergic neurotoxicity resulting from the Parkinson's-like inducing agent
Dluzen D E
Brain research
1996
1996-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0006-8993(95)01566-3" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(95)01566-3</a>
Estrogen alters MPTP-induced neurotoxicity in female mice: effects on striatal dopamine concentrations and release.
*MPTP Poisoning; 3; 4-Dihydroxyphenylacetic Acid/metabolism; Animals; Corpus Striatum/*drug effects/*metabolism; Dopamine/*metabolism; Estradiol/*pharmacology; Female; Inbred C57BL; Inbred Strains; Levodopa/pharmacology; Mice; Osmolar Concentration; Ovariectomy
The effects of estrogen on MPTP-induced neurotoxicity of the nigrostriatal dopaminergic system were examined in C57Bl and CD-1 mice. Ovariectomized mice with and without estrogen were treated with MPTP or its vehicle. The effects of these treatments on striatal dopamine concentrations and L-DOPA-stimulated dopamine and L-3,4-dihydroxyphenylacetic acid (DOPAC) release in vitro were determined. Dopamine concentrations of C57Bl mice receiving estrogen before MPTP were significantly greater than those of non-estrogen-treated MPTP mice as well as estrogen-treated mice receiving the MPTP vehicle. Dopamine concentrations of the CD-1 mice did not differ with these treatments. L-DOPA-evoked dopamine release values of estrogen-treated C57Bl mice were significantly increased compared with non-estrogen-treated mice. No such differences were observed in the
Dluzen D E; McDermott J L; Liu B
Journal of neurochemistry
1996
1996-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1046/j.1471-4159.1996.66020658.x" target="_blank" rel="noreferrer noopener">10.1046/j.1471-4159.1996.66020658.x</a>
Estrogen And Parkinson's Disease
alpha-synuclein gene; antiphospholipid antibodies; brain dopamine; dopamine; female rats; gender differences; nigrostriatal dopaminergic system; oral-contraceptives; postmenopausal women; sex-differences; striatal
Horstink Mwim; Strijks E; Dluzen D E
Parkinson's Disease
2003
2003
Book Chapter
n/a
Estrogen as a neuromodulator of MPTP-induced neurotoxicity: effects upon striatal dopamine release.
*MPTP Poisoning; 1-Methyl-4-phenylpyridinium/toxicity; Animals; Dopamine Agents/*toxicity; Dopamine/*metabolism; Estradiol/pharmacology; Estrogens/*physiology; Female; Neostriatum/drug effects/*metabolism; Neurotransmitter Agents/*physiology; Ovariectomy; Rats; Sprague-Dawley
The effects of estrogen upon MPTP-induced neurotoxicity were examined using in vitro superfusion. In Experiment 1, striatal tissue from ovariectomized rats was infused with MPP+ (10 microM), a combination of MPP+ and 17beta-estradiol (300 nM), the same dose of estradiol preceding MPP+, or no treatment infusion. The effects of these treatments on dopamine release rates during the infusion periods were determined. Infusion of MPP+ resulted in a significant increase in dopamine release as compared to the control. Estradiol added to the MPP+ infusion significantly attenuated this dopamine (DA) release, while estradiol treatment preceding the MPP+ had no effect. In Experiment 2, three different doses of estradiol (0.3, 3, or 300 nM) were infused simultaneously with the MPP+. Doses of estradiol below 300 nM did not attenuate the DA release. In Experiment 3, estradiol alone (300 nM) was infused, to determine dopamine release rate effects of the hormone itself. There was no difference between estradiol treated and non-infused control groups. These results demonstrate that the gonadal steroid hormone estradiol can modulate responses of striatal dopamine neurons to MPP+ by altering the immediate increase in dopamine release which occurs in response to this neurotoxin. These modulating effects of estradiol are dose-dependent, and represent a direct effect upon striatal neurons, most likely involving a non-genomic mechanism of action. These results implicate that hormonal modulation of nigrostriatal dopaminergic neurotoxicity may represent an important variable responsible for the sex differences which are reported in Parkinson's disease.
Disshon K A; Dluzen D E
Brain research
1997
1997-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(97)00418-6" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(97)00418-6</a>
Estrogen as a neuroprotectant against MPTP-induced neurotoxicity in C57/B1 mice.
*MPTP Poisoning; Animals; Corpus Striatum/drug effects/*metabolism/pathology; Dopamine/*metabolism; Drug Implants; Estradiol/administration & dosage/*pharmacology; Female; Inbred C57BL; Male; Mice; Neuroprotective Agents/administration & dosage/*pharmacology; Neurotoxins; Olfactory Pathways/drug effects/*metabolism/pathology; Orchiectomy; Ovariectomy; Sex Characteristics
Castrated retired breeder male and female mice were treated or not with a 17 beta-estradiol pellet. At 10 days postcastration +/- estrogen treatment all animals were treated with MPTP. Five days later, concentrations of dopamine were determined from the corpus striatum and olfactory tubercle. Both castrated male and female mice treated with estrogen had significantly greater concentrations of dopamine within the corpus striatum compared with their respective gender controls, which did not receive estrogen. By contrast, no statistically significant differences in olfactory tubercle dopamine concentrations were obtained. Overall concentrations of dopamine within the corpus striatum, but not olfactory tubercle, were substantially greater in female vs. male mice. These data demonstrate that treatment with estrogen prevents reductions in corpus striatal dopamine concentrations in castrated mice treated with MPTP. Interestingly, this effect of estrogen was observed in both male and female mice. These results suggest that estrogen may serve as a neuroprotectant against an agent that is toxic to the nigrostriatal dopaminergic system in both male and female animal models of Parkinsonism.
Dluzen D E; McDermott J L; Liu B
Neurotoxicology and teratology
1996
1996-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/0892-0362(96)00086-4" target="_blank" rel="noreferrer noopener">10.1016/0892-0362(96)00086-4</a>
Estrogen differentially modulates nicotine-evoked dopamine release from the striatum of male and female rats.
Animals; Corpus Striatum/drug effects/*metabolism; Dopamine/*metabolism; Estradiol/*pharmacology; Female; In Vitro Techniques; Kinetics; Male; Nicotine/*pharmacology; Orchiectomy; Ovariectomy; Rats; Sex Characteristics; Sprague-Dawley
In the present experiment we examined the effects of an in vitro infusion of nicotine (10 microM) upon dopamine release from superfused striatum of castrated male and female rats treated or not treated with estrogen. Estrogen exerted bidirectional effects on nicotine-evoked dopamine release as a function of the sex of the animal. Nicotine-evoked dopamine release was increased in estrogen treated females and decreased in estrogen treated males. Peak nicotine-evoked dopamine output from estrogen treated females was significantly greater than that of estrogen treated males. These results may be related to the gender differences in response to nicotine and smoking behavior.
Dluzen D E; Anderson L I
Neuroscience letters
1997
1997-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0304-3940(97)00487-4" target="_blank" rel="noreferrer noopener">10.1016/s0304-3940(97)00487-4</a>
Estrogen modulates responses of striatal dopamine neurons to MPP+: evaluations using in vitro and in vivo techniques
Neurosciences & Neurology; transporter; brain; neurotoxicity; Neuroprotection; cd-1 mice; nucleus-accumbens; sex-differences; estradiol; mptp-induced neurotoxicity; nigrostriatal; release; 17-beta-estradiol; anesthetized rat; electrochemistry; rat dorsal striatum; superfusion
In vitro superfusion and in vivo electrochemistry were used to investigate the role of estrogen in modulatings MPP+-induced dopamine output in the corpus striatum and nucleus accumbens of ovariectomized female rats. For in vitro superfusion experiments, dopamine and dihydroxyphenylacetic acid release were determined using HPLC with electrochemical detection from superfusion of corpus striatum fragments with Kreb's ringer phosphate buffer pulsed with MPP+ alone or MPP+ with estrogen. The in vivo electrochemistry experiments recorded the dopamine signal from carbon fiber microelectrodes stereotaxically passed through the corpus striatum and nucleus accumbens. Dopamine release was stimulated by pressure ejection of MPP+ alone or in combination with estrogen through glass micropipettes fastened to the electrodes. Dopamine output from superfusion chambers which received infusion of MPP+ with estrogen showed significantly lower output of dopamine compared with chambers which received MPP+ alone. Outputs of dihydroxyphenylacetic acid did not increase following MPP+ infusions. Data from the electrochemistry experiments demonstrated that estrogen significantly reduced both the amplitude and clearance rates of the MPP+-evokrd dopamine signal in both the corpus striatum and nucleus accumbens. Results of this study demonstrate that: (1) MPP+ evokes striatal dopamine release and this effect is significantly reduced in the presence of estrogen as determined by both in vivo electrochemistry and in vitro superfusion: (2) similar, albeit attenuated effects are observed in the nucleus accumbens as determined with in vivo electrochemistry; (3) estrogen acts to inhibit the clearance of dopamine in both the striatum and nucleus accumbens: and (4) estrogen may function as a neuroprotectant by reducing the uptake of neurotoxin into dopaminergic neurons. (C) 2000 Elsevier Science B.V. All rights reserved.
Arvin M; Fedorkova L; Disshon K A; Dluzen D E; Leipheimer R E
Brain Research
2000
2000-07
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/s0006-8993(00)02511-7" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(00)02511-7</a>
Estrogen prevents neuroprotection by caffeine in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease
adenosine; adenosine A(2A) receptor; c57bl/6 mice; coffee consumption; cytochromes p450; dopamine; estradiol; gender; methylxanthine; mptp-induced neurotoxicity; Neurosciences & Neurology; ovariectomy; risk; striatal dopamine; striatum; twins
Epidemiological studies have strongly linked caffeine consumption with a reduced risk of developing Parkinson's disease (PD) in men. Interestingly, in women, this inverse association is present only in those who have not taken postmenopausal estrogens, suggesting an interaction between the influences of estrogen and caffeine use on the risk of PD. To explore a possible biological basis for this interaction, we systematically investigated how the neuroprotective effect of caffeine is influenced by gender, ovariectomy (OVX), and then exogenous estrogen in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. (1) Caffeine treatment produced a dose-dependent attenuation of MPTP-induced striatal dopamine loss in both young and retired breeder (RB) male, but not female, mice. (2) In female mice (both young and RB), caffeine was less potent or altogether ineffective as a neuroprotectant after sham surgery compared to OVX or after OVX plus estrogen replacement compared to OVX plus placebo treatment. (3) Estrogen treatment also prevented the protection of caffeine against dopamine loss in young male mice. (4) Consistent with the putative protective effect of estrogen, female and OVX plus estrogen mice were relatively resistant to MPTP toxicity compared to male and OVX plus placebo mice, respectively. (5) There was no overall difference in brain levels of caffeine and its metabolites between OVX plus placebo and OVX plus estrogen mice. Together, these results suggest that estrogen can occlude and thereby prevent the neuroprotective effect of caffeine in a model of PD neurodegeneration, supporting a biological basis for the interaction between estrogen and caffeine in modifying the risk of PD.
Xu K; Xu Y H; Brown-Jermyn D; Chen J F; Ascherio A; Dluzen D E; Schwarzschild M A
Journal of Neuroscience
2006
2006-01
Journal Article
<a href="http://doi.org/10.1523/jneurosci.3008-05.2006" target="_blank" rel="noreferrer noopener">10.1523/jneurosci.3008-05.2006</a>
Estrogen Protects, But Does Not Restore, Nigrostriatal Dopaminergic Function In Methamphetamine Treated Mice
Biochemistry & Molecular Biology; Cell Biology; Life Sciences & Biomedicine - Other; Topics
Gao X; Dluzen D E
Faseb Journal
2000
2000-05
Journal Article or Conference Abstract Publication
n/a
Estrogen reduces acute striatal dopamine responses in vivo to the neurotoxin MPP+ in female, but not male rats.
*Sex Characteristics; 1-Methyl-4-phenylpyridinium/*toxicity; 3; 4-Dihydroxyphenylacetic Acid/metabolism; Animals; Corpus Striatum/*metabolism; Dopamine/*metabolism; Estrogens/*pharmacology; Extracellular Space/metabolism; Female; Herbicides/*toxicity; Male; Microdialysis; Nerve Degeneration/chemically induced/metabolism; Parkinson Disease; Rats; Secondary/chemically induced/metabolism; Sprague-Dawley
The effects of in vivo estrogen treatment upon MPP(+)-induced dopamine (DA) release were determined using in vivo microdialysis in female and male rats. Ovariectomized female rats were implanted or not with an estrogen pellet (0.1 mg, 17beta estradiol) and subjected to microdialysis 6 days later. After baseline DA release was determined, 5 mM MPP(+) was infused through the microdialysis probe for one 20-min interval. Perfusion resumed with normal medium for the duration of the experiment. A significant attenuation of MPP(+)-induced DA release was obtained in estrogen-treated females. One week later, striatal DA and dihydroxyphenylacetic acid (DOPAC) concentrations were determined for the lesioned and non-lesioned striata of each animal. MPP(+) infusion significantly decreased striatal DA concentrations, however, there was no effect of estrogen treatment on striatal DA depletion. This experiment was repeated using orchidectomized male rats treated with 0, 0.1, or 5 mg estradiol. In contrast to the females, no differences in MPP(+)-induced DA release were seen among these males, and there was no significant effect of the varying estrogen treatments on striatal DA or DOPAC concentrations. These results demonstrate that in vivo estrogen treatment attenuates MPP(+)-induced striatal DA release in gonadectomized female, but not male, rats.
Disshon K A; Dluzen D E
Brain research
2000
2000-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0006-8993(00)02329-5" target="_blank" rel="noreferrer noopener">10.1016/s0006-8993(00)02329-5</a>
Estrogen, Anti-estrogen, And Gender - Differences In Methamphetamine Neurotoxicity
breast cancer; dopamine; environmental-temperature; GFAP; in-vivo; mediated neuroprotection; mptp-induced neurotoxicity; nigrostriatal; nigrostriatal dopaminergic system; PAI-1; parkinsons-disease; parkinsons-disease; rat-brain; sex-differences; sexual differences; striatal dopamine; tamoxifen; testosterone; thermoregulation
Dluzen D E; McDermott J L
Cellular and Molecular Mechanisms of Drugs of Abuse Ii: Cocaine, Substituted Amphetamines, Ghb, and Opiates
2002
2002
Book Chapter
n/a
Estrogen, but not testosterone, attenuates methamphetamine-evoked dopamine output from superfused striatal tissue of female and male mice.
Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Estrogens/*metabolism; Female; In Vitro Techniques; Male; Methamphetamine/*pharmacology; Mice; Orchiectomy; Ovariectomy; Perfusion; Testosterone/*metabolism
The gonadal steroid hormone, estrogen, has the capacity to function as a neuroprotectant against methamphetamine (MA)-induced neurotoxicity of the nigrostriatal dopaminergic system within female, but not male, mice. In an attempt to understand some of the bases for this effect of estrogen, the incipient effects of MA upon evoked dopamine output from superfused striatal tissue fragments of gonadectomized female and gonadectomized as well as intact male mice were evaluated under conditions where estrogen (or testosterone) was present in the medium. The amount of dopamine evoked by MA was significantly reduced when estrogen was co-infused with MA. This attenuation was obtained with striatal tissue fragments of gonadectomized female and gonadectomized and intact male mice. In contrast to estrogen, co-infusion of testosterone failed to produce an overall statistically significant change in MA-evoked dopamine output within superfused striatal tissue fragments of gonadectomized female and male mice. In this way, the gonadal steroid hormones, estrogen and testosterone, exert differential modulatory effects upon MA-evoked dopamine output from superfused striatal tissue fragments. However, similar effects to these gonadal steroid hormones were observed between gonadectomized female and gonadectomized or intact male mice. These data reveal an absence of a sexual dimorphism in striatal responsiveness with regard to estrogen's ability to alter MA-evoked DA output. Accordingly, the sexually dimorphic capacity for estrogen to function as a neuroprotectant may involve a composite of actions upon the nigrostriatal dopaminergic system involving events/sites other than the initial stimulation of dopamine output.
Myers R E; Anderson L I; Dluzen D E
Neuropharmacology
2003
2003-04
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0028-3908(03)00043-1" target="_blank" rel="noreferrer noopener">10.1016/s0028-3908(03)00043-1</a>
Estrogen, Testosterone, And Methamphetamine Toxicity
17-beta-estradiol; c57/b1 mice; differences; female; gonadal steroids; inhibition; mptp-induced neurotoxicity; neurodegeneration; neuroprotection; neurotoxicity; nigrostriatal; nigrostriatal dopaminergic system; parkinsons-disease; sex; sexual differences; striatum; tamoxifen
Dluzen D E; McDermott J L
Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity: Cocaine, Ghb, and Substituted Amphetamines
2006
2006
Book Chapter
n/a
Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.
Animals; Body Weight/genetics; Brain-Derived Neurotrophic Factor/*deficiency/genetics/*metabolism; Corpus Striatum/*metabolism; Dopamine/*metabolism; Heterozygote; Homozygote; Hypothalamus/metabolism; Methamphetamine/pharmacology; Mice; Motor Activity/drug effects/physiology; Mutant Strains; Norepinephrine/metabolism; Olfactory Bulb/metabolism; Organ Specificity; Substantia Nigra/*metabolism; Walking/physiology
Deletion of a single copy of the BDNF gene has been shown to affect the nigrostriatal dopaminergic system of young adult BDNF mice. In the present report we evaluated various indices of nigrostriatal dopaminergic function between
Dluzen D E; Gao X; Story G M; Anderson L I; Kucera J; Walro J M
Experimental neurology
2001
2001-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1006/exnr.2001.7698" target="_blank" rel="noreferrer noopener">10.1006/exnr.2001.7698</a>
Gender differences in methamphetamine use and responses: A review.
Female; Male; Animals; Sex Factors; Gender Identity; Reproduction; Animal Studies; Substance Use Disorders; Central Nervous System Stimulants – Pharmacodynamics; Central Nervous System Stimulants – Pharmacokinetics; Depression – Drug Therapy; Methamphetamine – Pharmacodynamics; Methamphetamine – Pharmacokinetics
Background: Men and women differ markedly with regard to their use of, and responses to, methamphetamine (MA) and related amphetamines. However, these gender differences oftentimes are given only a cursory consideration in the analyses of these MA effects. Objective: In this brief review, we summarize the data on gender differences in various parameters of MA use and responses. Such information on the pattern of male versus female differences in the use and responses to this psychostimulant can aid in tailoring gender-dependent treatment strategies. Methods: English-language articles were identified from MEDLINE as well as from reference lists of identified articles for the years 1966 to 2007. Search terms included various combinations of men/male, women/female, methamphetamine, and gender/sex differences. Only studies with human subjects were reviewed. Results: Women tend to begin MA use at earlier ages, appear more dependent on MA, but also respond better to treatment than do men. MA use appears to be associated with depression in women, and women seem more committed to MA, whereas men are more likely to use other drugs in the absence of access to MA. Female MA abusers had both larger volumes within the corpus callosum and more hyperperfused regions in the parietal and occipital areas of the brain, along with more genetic alterations but less MA-induced toxicity. Amphetamine-stimulated dopamine release was greater in men. Conclusions: When considered in total, women seem more dependent on and committed to MA but show diminished (amphetamine-stimulated) dopamine responses and a decreased degree of toxicity, as indicated by a lower incidence of emergency department-related deaths involving MA. A pervasive comorbidity of depression or depression-related characteristics were present in women MA users, suggesting that MA may serve as a type of self-medication for their depression. These findings not only highlight the need for consideration of gender when assessing MA use, but also can serve to direct efforts at prevention and treatment programs that address the specific needs of men and women.
Dluzen D E; Liu B
Gender Medicine
2008
2008-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s1550-8579(08)80005-8" target="_blank" rel="noreferrer noopener">10.1016/s1550-8579(08)80005-8</a>
Gender differences in neurotoxicity of the nigrostriatal dopaminergic system: implications for Parkinson's disease.
Female; Humans; Male; Sex Factors; Sex Distribution; Estrogens/*pharmacology; Dopamine/metabolism; Postmenopause; Corpus Striatum/pathology/*physiopathology; Neurotoxins/*antagonists & inhibitors; Parkinson Disease/metabolism/pathology/*physiopathology; Substantia Nigra/pathology/*physiopathology; Animal; Disease Models
This article describes the progression of steps followed to demonstrate a gender difference associated with Parkinson's disease (PD) and to gain an understanding of the basis, mechanisms, and implications of this gender specificity. First, a review of the literature on PD shows a greater incidence in men. Next, data are presented from a series of laboratory studies in animal models of PD that suggest a basis for this gender difference: estrogen appears to act as a neuroprotectant of the striatal dopaminergic system. One mechanism for this effect may be that estrogen inhibits the uptake of neurotoxins capable of producing degeneration within dopaminergic neurons. Finally, some of the potential neurologic implications of manipulating estrogen in premenopausal and postmenopausal women are considered.
Dluzen D E; McDermott J L
The journal of gender-specific medicine : JGSM : the official journal of the Partnership for Women's Health at Columbia
2000
2000-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).