Castration increases nisoxetine-evoked norepinephrine levels in vivo within the olfactory bulb of male rats.
Animal/drug effects/physiology; Animals; Atomoxetine Hydrochloride; Extracellular Space/metabolism; Fluoxetine/*analogs & derivatives/*pharmacology; Male; Microdialysis; Norepinephrine Plasma Membrane Transport Proteins; Norepinephrine/*metabolism; Olfactory Bulb/drug effects/*metabolism; Orchiectomy/*adverse effects; Presynaptic Terminals/drug effects/metabolism; Propylamines/pharmacology; Rats; Reproduction/*physiology; Sexual Behavior; Smell/drug effects/physiology; Sprague-Dawley; Symporters/antagonists & inhibitors/*metabolism; Testosterone/*deficiency/metabolism; Up-Regulation/drug effects/physiology
In the present experiment we compared differences in extracellular norepinephrine levels in vivo within the olfactory bulb of intact and castrated male rats following infusion of the norepinephrine transport inhibitors, nisoxetine and tomoxetine. With this approach it was possible to assess whether dynamic changes in in vivo norepinephrine transporter function occur as a function of the gonadal state of the animal. Norepinephrine levels following infusion of nisoxetine were significantly increased in castrated compared with intact male rats. While a similar trend was present in response to tomoxetine infusion, these differences failed to achieve a statistically significant difference. These results demonstrate that castration of male rats alters norepinephrine transporter function within the olfactory bulbs. The increased extracellular levels of norepinephrine in response to agents which inhibit transporter function suggest that castration reduces transporter activity. Such effects have important implications not only with regard to processes involving the norepinephrine system in the olfactory bulb but also to the generalized sites and mechanisms by which gonadal steroid hormones modulate central nervous system functions.
Shang Yili; Dluzen Dean E
Neuroscience letters
2002
2002-08
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/s0304-3940(02)00412-3" target="_blank" rel="noreferrer noopener">10.1016/s0304-3940(02)00412-3</a>
DOPAMINERGIC MODULATION OF GLUTAMATE RELEASE IN STRIATUM AS MEASURED BY MICRODIALYSIS
afferents; amino-acid neurotransmitters; aspartate; Biochemistry & Molecular Biology; brain-tissue; corticostriatal path; d2 receptors; dopamine; endogenous glutamate; glutamate; in-vivo; lesion; microdialysis; nerve-terminals; Neurosciences & Neurology; pathway; rat caudate-putamen
Glutamate and aspartate are the primary neurotransmitters of projections from motor and premotor cortices to the striatum. Release of glutamate may be modulated by dopamine receptors located on corticostriatal terminals. The present study used microdialysis to investigate the dopaminergic modulation of in vivo striatal glutamate and aspartate release in the striatum of awake-behaving rats. Local perfusion with a depolarizing concentration of K+ through a dialysis probe into the rat striatum produced a significant increase in the release of glutamate, aspartate, and taurine. The D2 agonist LY171555 blocked the K+-induced release of glutamate and aspartate, but not taurine, in a concentration-dependent manner. The D1 agonist SKF 38393 did not alter K+-induced release of glutamate and taurine, but did significantly decrease aspartate release. Neither agonist had any effect on basal amino acid release. The D2 antagonist (-)-sulpiride reversed the inhibitory effects of LY 171555 on K+-induced glutamate release. These results provide in vivo evidence for a functional interaction between dopamine, the D2 receptor, and striatal glutamate release.
Yamamoto B K; Davy S
Journal of Neurochemistry
1992
1992-05
Journal Article
<a href="http://doi.org/10.1111/j.1471-4159.1992.tb10048.x" target="_blank" rel="noreferrer noopener">10.1111/j.1471-4159.1992.tb10048.x</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>
Inducible Nitric Oxide Inhibitors Block NMDA Antagonist-Stimulated Motoric Behaviors and Medial Prefrontal Cortical Glutamate Efflux.
schizophrenia; ataxia; green tea; iNOS; microdialysis; nNOS; phencyclidine; stereotypy
Nitric oxide (NO) plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA)-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase inhibitors (nNOS) for studying the neurobehavioral effects of non-competitive NMDA-antagonist stimulants such as dizocilpine (MK-801) and phencyclidine (PCP). This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS) aminoguanidine (AG) and (-)-epigallocatechin-3-gallate (EGCG) in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate e ffl ux. Adult male rats were administered a dose range of AG, EGCG, or vehicle prior to receiving NMDA antagonists MK-801, PCP, or a conventional psychostimulant (cocaine) and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated mPFC glutamate e ffl ux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate e ffl ux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in "green tea" and chocolate) may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.
Bergstrom Hadley C; Darvesh Altaf S; Berger S P
Frontiers in pharmacology
2015
1905-07
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/10.3389/fphar.2015.00292" target="_blank" rel="noreferrer noopener">10.3389/fphar.2015.00292</a>
Metabolic And Transmitter Changes In Core And Penumbra After Middle Cerebral Artery Occlusion In Mice
acetylcholine; Choline; focal ischemia; Glucose; glutamate; glutamate; Glycerol; hippocampus; hippocampus; intracerebral microdialysis; Microdialysis; mutant mice; neurodegenerative disorders; Neurosciences & Neurology; rat; release; reperfusion; Striatum; stroke
Middle cerebral artery occlusion (MCAO) is a popular model in experimental stroke research and causes prominent ischemic damage in the forebrain. To characterize metabolic changes induced by MCAO, we have induced permanent MCAO in mice that were implanted with a microdialysis probe in either striatum or hippocampus. Immediately after the onset of ischemia, glucose levels dropped to <10% of basal values in the striatum while they dropped to 50%, and recovered thereafter, in hippocampus. Extracellular levels of glutamate rose 80-fold in the striatum but only 10-fold, and in a transient fashion, in hippocampus. In striatum, release of acetylcholine briefly increased, then dropped to very low values. Both glycerol and choline levels increased strongly during ischemia in the striatum reflecting membrane breakdown. In hippocampus, glycerol increased transiently while the increase of choline levels was moderate. Taken together, these observations delineate metabolic changes in ischemic mouse brain with the striatum representing the core area of ischemia. In comparison, the dorsal hippocampus was identified as a brain area suitable for monitoring metabolic responses in the penumbra region. (C) 2009 Elsevier B.V. All rights reserved.
Kiewert C; Mdzinarishvili A; Hartmann J; Bickel U; Klein J
Brain Research
2010
2010-02
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.brainres.2009.11.068" target="_blank" rel="noreferrer noopener">10.1016/j.brainres.2009.11.068</a>
Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-induced Glutamate Release In Vivo
brain-injury; cerebral-artery occlusion; extract egb-761; Ginkgo biloba; Ginkgo biloba; Glucose; inhibition; mice; Microdialysis; Microdialysis; Middle cerebral artery occlusion; Neurosciences & Neurology; phospholipid breakdown; sensorimotor; stroke; stroke
Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40-50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the striatum which returned to baseline levels after reperfusion. Extracellular levels of glutamate were increased by more than ten-fold in striatal tissue, and by four- to fivefold in hippocampal tissue (penumbra). Bilobalide did not affect glucose levels but strongly attenuated glutamate release in both core and penumbra regions. Bilobalide was equally active when given locally via the microdialysis probe and also reduced ischemia-induced glutamate release in vitro in brain slices. We conclude that bilobalide is a strong neuroprotectant in vivo at doses that can be used therapeutically in humans. The mechanism of action evidently involves reduction of glutamate release, thereby reducing excitotoxicity. (C) 2011 Elsevier B.V. All rights reserved.
Lang D; Kiewert C; Mdzinarishvili A; Schwarzkopf T M; Sumbria R; Hartmann J; Klein J
Brain Research
2011
2011-11
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/j.brainres.2011.10.005" target="_blank" rel="noreferrer noopener">10.1016/j.brainres.2011.10.005</a>
Oxytocin induces preservation of social recognition in male rats by activating alpha-adrenoceptors of the olfactory bulb.
Male; Animals; *Social Behavior; Rats; Adrenergic beta-Antagonists/pharmacology; Adrenergic beta-Agonists/pharmacology; Microdialysis; Adrenergic alpha-Antagonists/pharmacology; Phentolamine/pharmacology; Isoproterenol/pharmacology; Clonidine/pharmacology; Norepinephrine/pharmacology; Social Dominance; Adrenergic alpha-Agonists/pharmacology; Memory/*drug effects/physiology; Olfactory Bulb/*drug effects/physiology; Oxytocin/*pharmacology; Timolol/pharmacology; Receptors; Adrenergic; Wistar; alpha/*drug effects/physiology; Oxytocin/drug effects/*physiology
In this report, a series of four experiments was performed to evaluate the relationship between the olfactory bulb norepinephrine system and intra-olfactory bulb infusion of oxytocin in the preservation of social memory responses. The present data indicate that oxytocin exerts this preservation of social recognition through a specific, receptor-mediated mechanism within the olfactory bulb (experiment 1). The involvement of the olfactory bulb norepinephrine system is revealed by the demonstration that retrodialysis of oxytocin into the olfactory bulb increases norepinephrine release (experiment 4). Our data suggest that the increased output of olfactory bulb norepinephrine resulting from oxytocin appears to activate alpha-adrenoceptors to produce this preservation in recognition because infusions of clonidine into the olfactory bulb preserve recognition responses in a manner similar to that observed with oxytocin (experiment 2). In addition, a co-infusion of oxytocin with phentolamine abolishes recognition responses (experiment 3). Accordingly, this model affords the opportunity to study neuropeptide-catecholamine interactions, link these interactions with a specific behavioural outcome and identify a novel function/site of action for oxytocin in the male.
Dluzen D E; Muraoka S; Engelmann M; Ebner K; Landgraf R
The European journal of neuroscience
2000
2000-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
The effect of GDNF on nigrostriatal dopaminergic function in response to a two-pulse K(+) stimulation.
*Nerve Growth Factors; 3; 4-Dihydroxyphenylacetic Acid/metabolism; Animals; Corpus Striatum/*drug effects/metabolism; Dopamine/*metabolism; Dose-Response Relationship; Drug; Extracellular Space/metabolism; Glial Cell Line-Derived Neurotrophic Factor; Male; Microdialysis; Nerve Tissue Proteins/*pharmacology; Neuroprotective Agents/*pharmacology; Parkinson Disease/drug therapy/metabolism; Potassium/*pharmacology; Rats; Sprague-Dawley; Substantia Nigra/*drug effects/metabolism
We examined the effect of glial cell line-derived neurotrophic factor (GDNF) upon nigrostriatal dopaminergic function in response to two-pulse potassium (K(+)) stimulation in rats under in vivo microdialysis conditions. The two-pulse infusion protocol permits us to focus upon the role of this neurotrophin as related to vesicular storage and release of dopamine (DA). The effects of two
Xu K; Dluzen D E
Experimental neurology
2000
2000-12
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.2000.7515" target="_blank" rel="noreferrer noopener">10.1006/exnr.2000.7515</a>