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>
A comparative analysis of monoaminergic involvement in the spinal antinociceptive action of DAMPGO and DPDPE.
Male; Animals; Rats; Injections; Enkephalins/*pharmacology; Naloxone/pharmacology; Anesthetics/*pharmacology; Biogenic Monoamines/*physiology; Pain/*metabolism; Spinal Cord/drug effects/metabolism/*physiopathology; Dose-Response Relationship; Drug; Inbred Strains; Receptors; Enkephalin; Ala(2)-MePhe(4)-Gly(5)-; Spinal; 5)-; D-Penicillamine (2; Opioid/drug effects/*physiology; Enkephalins; Intraspinal; Amines – Physiology; Anesthetics – Pharmacodynamics; Cell Surface – Drug Effects; Cell Surface – Physiology; Enkephalins – Pharmacodynamics; Naloxone – Pharmacodynamics; Pain – Metabolism; Spinal Cord – Drug Effects; Spinal Cord – Metabolism; Spinal Cord – Physiopathology
The antinociceptive properties of intrathecally (i.t.) administered [D-Ala2,
Spanos L J; Stafinsky J L; Crisp T
Pain
1989
1989-12
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/10.1016/0304-3959(89)90046-8" target="_blank" rel="noreferrer noopener">10.1016/0304-3959(89)90046-8</a>
A neurochemical heterogeneity of the rat striatum as measured by in vivo electrochemistry and microdialysis.
Male; Animals; Rats; Dopamine/*metabolism; Corpus Striatum/*metabolism; Amphetamines/*pharmacology; Electrochemistry; Sulpiride/*pharmacology; Inbred Strains; Receptors; 3; 4-Dihydroxyphenylacetic Acid/metabolism; Dopamine/drug effects; Dopamine D2
The neurochemical heterogeneity of the rat striatum was assessed in vivo by measuring subregional changes in extracellular dopamine and DOPAC by in vivo electrochemistry and microdialysis in response to amphetamine and the D2 antagonist, (-)-sulpiride. Both in vivo electrochemical and microdialysis experiments indicated a significant rostrocaudal gradient in dopamine release following amphetamine. The increase in dopamine release was highest in the rostral areas (over 800% of baseline values) and lowest in the most caudal subregion (425% of baseline). No lateromedial differences in dopamine release were observed. DOPAC levels decreased in dialysates but were similar for all 6 subregions examined. In contrast, D2 blockade with (-)-sulpiride revealed a lateromedial gradient in the increases seen for dopamine and DOPAC such that greater increases were observed in the lateral subregions. (-)-Sulpiride did not produce any differential effects along the rostrocaudal axis. The regional gradients detected in extracellular fluid changes of dopamine and DOPAC indicate that dopamine release is locally regulated by an interaction between the density of dopaminergic innervation to a particular subregion and the D2 receptor density.
Yamamoto B K; Pehek E A
Brain research
1990
1990-01
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/10.1016/0006-8993(90)91256-g" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(90)91256-g</a>
A rapid and simple HPLC microassay for biogenic amines in discrete brain regions.
Male; Animals; Rats; Reference Values; Organ Specificity; *Brain Chemistry; Chromatography; Biogenic Amines/*analysis; Corpus Striatum/analysis; Indicators and Reagents; Nucleus Accumbens/analysis; Inbred Strains; High Pressure Liquid/methods
A rapid microassay is described for the measurement of biogenic amines using an isocratic HPLC system with electrochemical detection. Catecholamines, indoleamines and their major metabolites were extracted with 150 microliters of perchloric acid from brain tissue punches (less than 250 micrograms) using a simple one-step sample preparation method. These compounds were separated on a short (80 mm) column with 3 microns particle size packing, and electrochemically detected within a total run time of less than 6 minutes. Detection limit sensitivity was approximately 2-5 pg. This method, detailed in an easy-to-follow description, reduces assay time, minimizes the possibility for errors, maximizes efficiency, and requires only standard HPLC equipment and supplies.
Donzanti B A; Yamamoto B K
Pharmacology, biochemistry, and behavior
1988
1988-07
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/10.1016/0091-3057(88)90102-5" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(88)90102-5</a>
A slice preparation preserving the callosal projection to contralateral visual cortex.
Female; Male; Animals; Rats; *Synaptic Transmission; In Vitro Techniques; Electrophysiology; Corpus Callosum/*physiology; Neurology/instrumentation; Visual Cortex/*physiology; Inbred Strains
Due to the curved path they follow, the visual callosal projections to areas OC1 and OC2 of the rat visual cortex have been inaccessible to studies using brain slices. In this paper we describe a new slice preparation in which a curved cutting blade was used to obtain slices in which callosal fibers projecting to OC1 or OC2 are preserved. Stimulation of the contralateral white matter resulted in EPSPs recorded in layer II/III and V cells of OC2 studied with intracellular recording. Current source density analysis of extracellular field potentials collected in OC1 and OC2 revealed laminar current sink patterns paralleling the laminar distribution of callosal terminations reported by Miller and Vogt (Dev. Brain Res., 14 (1984) 304-309). Exposure of slices to 2 mM kynurenic acid reversibly abolished current sinks in OC1 recorded in response to callosal stimulation indicating that glutamate receptors mediate the response of OC1 to callosal afferent activity. This new slicing technique can be readily adapted to study other systems in the nervous system in which neural processes follow curved trajectories.
Berry R L; Nowicky A; Teyler T J
Journal of neuroscience methods
1990
1990-08
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/10.1016/0165-0270(90)90021-7" target="_blank" rel="noreferrer noopener">10.1016/0165-0270(90)90021-7</a>
Acute and subchronic effects of methylenedioxymethamphetamine [(+/-)MDMA] on locomotion and serotonin syndrome behavior in the rat.
Male; Time Factors; Animals; Rats; Behavior; Motor Activity/*drug effects; Amphetamines/*pharmacology; Designer Drugs/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; Receptors; 3; Animal/*drug effects; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; Serotonin/*drug effects
Specific behaviors comprising the serotonin syndrome (low body posture, forepaw treading, headweaving) and the autonomic signs of piloerection and salivation were determined and analyzed with locomotor activity in response to MDMA at three doses (2.5, 5.0, and 7.5 mg/kg). All behaviors were dose-responsive. Serotonin syndrome behaviors increased in both intensity and duration of response with increasing doses. In contrast, locomotion varied only in intensity. Subchronic injections, in the same group of animals, permitted an analysis of acute vs. subchronic effects on these same behaviors. Both the serotonin syndrome and locomotor behaviors were augmented on subsequent testing, indicating that, (+/-)MDMA, like amphetamine, is capable of producing behavioral sensitization.
Spanos L J; Yamamoto B K
Pharmacology, biochemistry, and behavior
1989
1989-04
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/10.1016/0091-3057(89)90044-0" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(89)90044-0</a>
Aflatoxin B1 metabolism by 3-methylcholanthrene-induced hamster hepatic cytochrome P-450s.
Animals; Rats; Gene Expression Regulation; Liver/enzymology; Antibodies/immunology; Cricetinae; Enzyme Induction/drug effects; Mesocricetus; Aflatoxin B1; Liver/drug effects/*enzymology; Methylcholanthrene/*pharmacology; Aflatoxins/immunology/*metabolism; Cytochrome P-450 Enzyme System/biosynthesis/isolation & purification/*metabolism; Mutagenicity Tests; Salmonella typhimurium/enzymology/genetics; Subcellular Fractions/drug effects/enzymology; Inbred Strains; Enzymologic; Microsomes
We have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P-450 isozymes using a umu mutagen test. The hamster liver microsomes or S-9 fractions were much more active than rat liver microsomes or S-9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3-Methyl-cholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3-methylcholanthrene-inducible cytochrome
Lai T S; Chiang J Y
Journal of biochemical toxicology
1990
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/10.1002/jbt.2570050303" target="_blank" rel="noreferrer noopener">10.1002/jbt.2570050303</a>
An improved and rapid HPLC-EC method for the isocratic separation of amino acid neurotransmitters from brain tissue and microdialysis perfusates.
Dialysis; Male; Animals; Rats; *Brain Chemistry; Chromatography; Electrochemistry; Corpus Striatum/analysis; Amino Acids/*analysis; Neurotransmitter Agents/*analysis; Inbred Strains; High Pressure Liquid/*methods
An improved, HPLC with electrochemical detection method for the isocratic separation and determination of amino acids from post-mortem brain tissue and from microdialysates of awake-behaving animals is described. Optimal conditions that maximize stability, resolution, and sensitivity were determined for the pre-column derivatization of amino acids using o-phthalaldehyde and
Donzanti B A; Yamamoto B K
Life sciences
1988
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/10.1016/0024-3205(88)90267-6" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(88)90267-6</a>
Analgesic effects of serotonin and receptor-selective serotonin agonists in the rat spinal cord.
Male; Animals; Rats; Pain Measurement; Piperazines/pharmacology; Spinal Cord/*physiology; Tetrahydronaphthalenes/pharmacology; Injections; Amphetamines/pharmacology; Biguanides/pharmacology; Serotonin Antagonists/pharmacology; Reaction Time/drug effects; *Analgesics; 8-Hydroxy-2-(di-n-propylamino)tetralin; Serotonin/*pharmacology; Inbred Strains; Receptors; Spinal; Serotonin/*drug effects/physiology
1. Serotonin (5-HT) and selective 5-HT receptor agonists were administered intrathecally (i.t.) in rats, and the antinociceptive efficacy of these agents was assessed on the tail-flick and hot plate tests. 2. The 5-HT receptor agonists examined in this study included the 5-HT1A agonist
Crisp T; Stafinsky J L; Spanos L J; Uram M; Perni V C; Donepudi H B
General pharmacology
1991
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/10.1016/0306-3623(91)90441-8" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(91)90441-8</a>
Analysis of connective tissues by laser capture microdissection and reverse transcriptase-polymerase chain reaction.
*Microdissection; Animals; Cell Separation/*methods; Chondrocytes/chemistry/cytology; Connective Tissue Cells/chemistry/*cytology; Gene Expression Profiling/*methods; Growth Plate/cytology; Inbred Strains; Lasers; Messenger/analysis/*isolation & purification; Methods; Mice; Newborn; Reverse Transcriptase Polymerase Chain Reaction; RNA; Tibia/cytology
Studies of gene expression from bone, cartilage, and other tissues are complicated by the fact that their RNA, collected and pooled for analysis, often represents a wide variety of composite cells distinct in individual phenotype, age, and state of maturation. Laser capture microdissection (LCM) is a technique that allows specific cells to be isolated according to their phenotype, condition, or other marker from within such heterogeneity. As a result, this approach can yield RNA that is particular to a subset of cells comprising the total cell population of the tissue. This study reports the application of LCM to the gene expression analysis of the cartilaginous epiphyseal growth plate of normal newborn mice. The methodology utilized for this purpose has been coupled with real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) to quantitate the expression of certain genes involved in growth plate development and calcification. In this paper, the approaches used for isolating and purifying RNA from phenotypically specific chondrocyte populations of the murine growth plate are detailed and illustrate and compare both qualitative and quantitative RT-PCR results. The technique will hopefully serve as a guide for the further analysis of this and other connective tissues by LCM and RT-PCR.
Jacquet Robin; Hillyer Jennifer; Landis William J
Analytical biochemistry
2005
2005-02
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/10.1016/j.ab.2004.09.033" target="_blank" rel="noreferrer noopener">10.1016/j.ab.2004.09.033</a>
Attenuation of drinking sweetened water following calcium channel blockade.
Animals; Calcium Channel Blockers/*pharmacology; Cocaine/pharmacology; Dihydropyridines/pharmacology; Dose-Response Relationship; Drinking Behavior/*drug effects; Drug; Female; Inbred Strains; Injections; Intraventricular; Isradipine; Male; Rats; Reward; Taste/*drug effects
Recent reports cite results that both cocaine-induced conditioned place preference and activity stimulation are attenuated by pretreatment with the calcium channel blocker isradipine (ISR) in rats. By blocking voltage-dependent
Calcagnetti D J; Schechter M D
Brain research bulletin
1992
1992-06
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/10.1016/0361-9230(92)90219-n" target="_blank" rel="noreferrer noopener">10.1016/0361-9230(92)90219-n</a>
Behavioral effects of N-ethyl-3,4-methylenedioxyamphetamine (MDE; "EVE").
Male; Time Factors; Animals; United States; Rats; Discrimination (Psychology); Amphetamines/*pharmacology; Dose-Response Relationship; Drug; Inbred Strains; 3; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/analogs & derivatives/*pharmacology; Legislation
Eight male rats were trained to discriminate 2.0 mg/kg
Boja J W; Schechter M D
Pharmacology, biochemistry, and behavior
1987
1987-10
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/10.1016/0091-3057(87)90206-1" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(87)90206-1</a>
Biphasic effects of ethanol tested with drug discrimination in HAD and LAD rats.
Alcohol Drinking/genetics/*psychology; Animals; Discrimination (Psychology)/*drug effects; Discrimination Learning/drug effects; Dose-Response Relationship; Drug; Ethanol/*pharmacology; Inbred Strains; Male; Pentobarbital/pharmacology; Rats; Serotonin Antagonists/pharmacology; Sleep/drug effects; Time Factors; Tropanes/pharmacology
Seventh-generation selectively bred high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats were trained to make differential responses for ethanol (0.75 g/kg, IP) and saline vehicle, following postadministration intervals (PI) of 2 min (HAD-2 and LAD-2 animals) and 30 min (HAD-30 and LAD-30 animals). ED50 values of 0.395 and 0.352 g/kg, respectively, for HAD-2 and LAD-2 animals and 0.269 and 0.314 g/kg, respectively, for HAD-30 and LAD-30 animals reflect the absence of any phenotypic difference for the discriminative stimulus effects of ethanol. HAD-2 animals were more responsive than LAD-2 animals to the stimulating effects of ethanol as measured by total response rates during training sessions. The differential ethanol response generalized to pentobarbital in all four groups but not to morphine, an alternative CNS depressant. The specific antagonist of 5-hydroxytryptamine3 receptors,
Krimmer E C
Pharmacology, biochemistry, and behavior
1992
1992-12
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/10.1016/0091-3057(92)90508-d" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(92)90508-d</a>
Brain reactive antibodies and the blood-brain barrier: observations in aging rodents and the effects of peripheral kainic acid.
Aging/*immunology/physiology; Animals; Autoantibodies/blood/*physiology; Blood-Brain Barrier/*drug effects; Brain/*immunology/physiology; Hippocampus/immunology/physiology; Inbred C57BL; Inbred Strains; Kainic Acid/*pharmacology; Male; Mice; Rats
This study was initiated to confirm the existence of brain-reactive autoantibodies and to determine if such antibodies have higher affinity for brain regions especially affected in Alzheimer's disease. Serum collected from 90, 300, and 600 day old mice was incubated against brain tissues from these same mice, followed by incubation with fluorescently tagged rabbit antimouse IgG. No antibodies were present in the youngest serum, but considerable antibodies were present at 300 and, especially, at 600 days. Such antibodies were present in the blood vessels, but not in the brains of older animals. These antibodies, applied exogenously, labeled cells equally in all three ages of brains including most cortical and many other neurons, indicating that they are not neurotransmitter specific. In a further study, kainic acid or saline was administered peripherally to 15-month old rats. Kainic acid damaged the blood brain barrier and allowed the CNS entry of brain-reactive antibodies, especially into the subregions of hippocampus most damaged in Alzheimer's.
Kulmala H K; Boja J W; Albrecht J W; Hutton J T
Experimental aging research
1987
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/10.1080/03610738708259303" target="_blank" rel="noreferrer noopener">10.1080/03610738708259303</a>
Castration reduces potassium-stimulated norepinephrine release from superfused olfactory bulbs of male rats.
*Orchiectomy; Animals; Inbred Strains; Kinetics; Male; Norepinephrine/*metabolism; Olfactory Bulb/drug effects/*physiology; Potassium/*pharmacology; Rats; Reference Values; Testosterone/*pharmacology
In order to investigate the possible relationship among the olfactory bulb (OB), norepinephrine (NE) and gonadal steroids, we measured NE release from superfused anterior and posterior OB in intact and castrated male rats (Expt. I) as well as in castrated male rats implanted with either empty or testosterone filled silastic capsules (Expt. II). Both basal and potassium (K+ 30 mM)-stimulated release of NE was greater in posterior compared to anterior OB. All groups were responsive to the K+ stimuli showing increases in NE release. The degree of K(+)-stimulated release was significantly greater in intact compared to that of castrated rats. No differences in K(+)-stimulated release were observed between castrated and castrated plus testosterone-treated groups. These results demonstrate that castration of male rats significantly reduces OB noradrenergic responsiveness to K+ stimulation, an effect which was not restored following administration of silastic capsules containing testosterone.
Guan X B; Dluzen D
Brain research
1991
1991-12
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/10.1016/0006-8993(91)91390-m" target="_blank" rel="noreferrer noopener">10.1016/0006-8993(91)91390-m</a>
Cloning and characterization of two major 3-methylcholanthrene inducible hamster liver cytochrome P450s.
Female; Humans; Male; Animals; Rats; Amino Acid Sequence; Reference Values; Base Sequence; Liver/enzymology; Immunoblotting; Molecular Sequence Data; Cricetinae; Mesocricetus; Phenobarbital/pharmacology; Restriction Mapping; Nucleic Acid Hybridization; Cytochrome P-450 Enzyme System/biosynthesis/*genetics; Enzyme Induction; Liver/drug effects/*enzymology; Methylcholanthrene/*pharmacology; Inbred Strains; Sequence Homology; Cloning; Molecular; Nucleic Acid; Microsomes
We have studied the immunochemical properties of two major 3-methylcholanthrene inducible hamster liver cytochrome P450 isozymes, P450 MC1 and P450 MC4. Immunoblots using specific antibodies against P450 MC1 and P450 MC4 demonstrated that these two P450s were present in very low levels in control hamster livers and were greatly induced by 3-methylcholanthrene treatment. P450 MC1 was immunochemically different from P450 MC4, rat P450c and P450d, and rabbit LM4. The immunorelated polypeptide to P450 MC1 was not present in the control or the
Lai T S; Chiang J Y
Archives of biochemistry and biophysics
1990
1990-12
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/10.1016/0003-9861(90)90664-k" target="_blank" rel="noreferrer noopener">10.1016/0003-9861(90)90664-k</a>
Cocaethylene-induced kindling of seizure effects: cross-specificity with cocaine.
Animals; Cocaine/*analogs & derivatives/pharmacology; Convulsants/*pharmacology; Dopamine Uptake Inhibitors/*pharmacology; Drug Interactions; Epilepsy; Female; Inbred Strains; Kindling; Male; Mice; Neurologic/*drug effects; Seizures/*chemically induced; Status Epilepticus/chemically induced; Tonic-Clonic/chemically induced
Sensitization and cross-sensitization to the seizurogenic effects of cocaine and cocaethylene were examined in the HS strain of mice. Animals were administered IP injections of either 48 mg/kg cocaine or 32 mg/kg cocaethylene once per day for 4 days. On the fifth day, mice were injected with either the same drug that was administered on days 1-4 or the alternative psychostimulant and the occurrence of seizure activity was recorded. Repeated cocaine administration resulted in the induction of tonic-clonic seizures and status epilepticus in 90% of the animals tested with cocaine on the fifth day. A similar increase in seizure prevalence, noted as a kindling effect, was observed in cocaethylene-treated animals tested with cocaethylene in that 90% of the mice exhibited status epilepticus on the last test day. Significant cross-sensitization was observed only in the group that received cocaethylene following repeated cocaine exposure. However, data obtained from animals injected with cocaine following cocaethylene treatment also were suggestive of cross-sensitization effects. Results are discussed in terms of the potential mechanistic differences between cocaine and its ethanol-derived product, as well as its relevance to cocaine use/abuse.
Meehan S M; Schechter M D
Pharmacology, biochemistry, and behavior
1996
1996-06
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/10.1016/0091-3057(95)02275-9" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(95)02275-9</a>
Cocaethylene-induced lethality in mice is potentiated by alcohol.
Animals; Cocaine/*analogs & derivatives/poisoning; Dose-Response Relationship; Drug; Drug Synergism; Ethanol/*pharmacology; Female; Inbred Strains; Lethal Dose 50; Male; Mice
Mice of the heterogeneously bred HS line were concurrently administered intraperitoneal injections of either 95, 75, 60, or 48 mg/kg cocaethylene or 48, 38, or 30 mg/kg cocaethylene in conjunction with the non-lethal dose of 6.0 g/kg (20% w/v) alcohol. Results indicate that alcohol administration significantly potentiated cocaethylene-induced lethality. This observation suggests that alcohol is capable of enhancing the lethal effects of cocaethylene. Results are discussed in terms of observations of sudden death in humans who abuse cocaine and alcohol.
Meehan S M; Schechter M D
Alcohol (Fayetteville, N.Y.)
1995
1995-08
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/10.1016/0741-8329(95)00022-j" target="_blank" rel="noreferrer noopener">10.1016/0741-8329(95)00022-j</a>
Comparison of anorectic drugs in rats trained to discriminate between satiation and deprivation.
Male; Animals; Rats; Analysis of Variance; Discrimination Learning/*drug effects; Amphetamine/*pharmacology; *Food Deprivation; Fenfluramine/*analogs & derivatives/*pharmacology; Norfenfluramine/*pharmacology; Satiation/*drug effects; Dose-Response Relationship; Drug; Inbred Strains
Eight male rats were trained to discriminate between the internal states produced by food deprivation of 3 hours (satiation) and that produced by food deprivation of 27 hours duration (deprivation). One lever, in a two-lever operant chamber, had to be pressed to receive reinforcement in the satiation state, whereas pressing the other lever was required when the rat was in the deprivation state. Once the rats were trained, increasing the number of hours of food deprivation, from 1 to 48 hours, resulted in more deprivation-appropriate lever responses in the two-lever operant task. Administration of doses of fenfluramine (0.5-1.5 mg.kg), its active metabolite norfenfluramine (0.25-1.0 mg/kg) or d-amphetamine (0.5-1.5 mg/kg) produced a dose-responsive decrease in deprivation-appropriate responses when each drug/dose was injected (i.p.) 15 min prior to deprivation (27 hours) testing. Norfenfluramine was 1.5 times more potent than fenfluramine which was 1.5 times more potent than amphetamine.
Schechter M D
Life sciences
1990
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/10.1016/0024-3205(90)90561-5" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(90)90561-5</a>
Conditioned place aversion following the central administration of a novel dopamine release inhibitor CGS 10746B.
Animals; Antipsychotic Agents/administration & dosage/*pharmacology; Avoidance Learning/*drug effects; Dopamine/*metabolism; Inbred Strains; Injections; Intraventricular; Male; Motor Activity/*drug effects; Rats; Thiazepines/administration & dosage/*pharmacology
Numerous drugs of abuse that elevate brain extracellular dopamine concentrations by either increasing the firing rate of dopaminergic neurons or producing dopamine release have been shown to reliably condition a preference for place. If dopamine release is a necessary component for conditioned place preference (CPP), one reciprocal hypothesis may be that inhibition of dopamine release will result in conditioned place aversion (CPA). This hypothesis has been tested pharmacologically by employing CGS 10746B (CGS), a novel neuroleptic known to inhibit the release of dopamine via presynaptic mechanisms. In previous work the peripheral administration of CGS (1.25-20 mg/kg) produced place aversion at doses above 5 mg/kg. However, the contribution of peripheral mechanisms in the production of CGS-induced CPA is unknown. To test whether central administration of CGS would also result in CPA, rats were fitted with chronic intraventricular cannula. Groups of rats subsequently received four conditioning trials with one of four intraventricular (ICV) doses of CGS (1-30 micrograms) when confined to their preferred side of a place conditioning apparatus. Vehicle was similarly administered on four interspersed days prior to confining these same rats to their nonpreferred side of the apparatus. At the conclusion of these eight conditioning trials, the rats were tested, on separate days, in a nondrugged and a CGS-drugged state. The highest dose of CGS (30 micrograms) produced a CPA as evidenced by rats spending less time in the environment initially found to be preferred. Locomotor activity was also measured over a 30-min period with and without ICV injection of CGS (1-30 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)
Calcagnetti D J; Schechter M D
Pharmacology, biochemistry, and behavior
1991
1991-10
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/10.1016/0091-3057(91)90548-g" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(91)90548-g</a>
Conditioned place preference/aversion to fenfluramine in fawn hooded and sprague-Dawley rats.
Animals; Avoidance Learning/*drug effects; Blood Platelets/metabolism; Brain Chemistry/genetics; Fenfluramine/*pharmacology; Habituation; Inbred Strains; Platelet Storage Pool Deficiency/physiopathology; Psychophysiologic/drug effects; Rats; Serotonin/metabolism/physiology; Species Specificity; Sprague-Dawley
The Fawn Hooded (FH) rat strain possesses a genetic platelet storage pool deficiency which leads to an impaired capacity for platelets to store and release serotonin. While the relationship between this deficit and possible alterations in brain serotonergic levels or function remains unclear, numerous behavioral studies have indicated that FH rats exhibit differential responses to serotonergic agonists and antagonist relative to other strains. The current study used the conditioned place preference paradigm to examine the ability of fenfluramine to produce a conditioned place preference (CPP) or aversion (CPA) in FH and Sprague-Dawley (SD) rats. Results indicated that fenfluramine failed to produce CPP or CPA in SD rats, but did produce a CPA in FH rats. Results are discussed in terms of the use of conditioned place preference to assess putative differences in serotonergic functioning in FH rats.
Meehan S M; Schechter M D
Progress in neuro-psychopharmacology & biological psychiatry
1994
1994-05
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/10.1016/0278-5846(94)90014-0" target="_blank" rel="noreferrer noopener">10.1016/0278-5846(94)90014-0</a>
Deficits in shock-induced freezing and naltrexone enhancement of freezing in fawn hooded rats.
*Fear; Animals; Classical/*drug effects; Conditioning; Electroshock; Female; Inbred Strains; Naltrexone/*pharmacology; Rats
When a rat is returned to a context associated with mild electric foot shock (1 mA/0.75 s), the environmental cues elicit a species-specific defensive behavior termed freezing. Genetically divergent strains of rats given identical shock conditioning differ in the degree of freezing observed. The acquisition of freezing appears to be mediated, at least in part, by endogenous opioids since the duration that a rat spends freezing is increased by pretreatment prior to training with naltrexone (NTX), an opioid receptor antagonist. The objective of the present studies was to compare the shock-induced freezing and its enhancement with NTX in two unique strains of rats, viz., N/Nih and Fawn Hooded (FH), with that seen in the more commonly employed Sprague-Dawley strain (SPD). Age-matched female rats from these three strains were observed for freezing after shock conditioning. Separate groups of rats from each strain were treated with NTX (7.0 mg/kg) prior to shock. Vehicle (VEH; 0.9% saline)-treated SPD and N/Nih rats were observed freezing for approximately 30% of the testing duration, whereas FH rats froze for only 15% of the test duration. NTX-treated SPD and N/Nih rats displayed an equivalent 130% increase in freezing in comparison to their respective saline controls. Freezing in NTX treated FH rats did not differ from VEH. Collectively, these results suggest that the level of freezing and NTX enhancement of freezing in the N/Nih rat strain are equivalent to SPD. In comparison, FH rats show deficits in freezing and are insensitive to NTX enhancement of freezing.
Calcagnetti D J; Schechter M D
Brain research bulletin
1994
1994
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/10.1016/0361-9230(94)90213-5" target="_blank" rel="noreferrer noopener">10.1016/0361-9230(94)90213-5</a>
Development of habituation in the dentate gyrus of rat: physiology and anatomy.
Female; Male; Animals; Rats; Synapses/physiology; Hippocampus/anatomy & histology/physiology; Inbred Strains; Habituation; Psychophysiologic/*physiology
The physiological development of monosynaptic response habituation in the rat dentate gyrus was compared to morphological development. Rapid Golgi techniques were coupled with in vitro studies of dentate granule cell habituation to several frequencies and intensities of monosynaptic excitation. Except for the youngest group, the degree of habituation increased as a function of age, paralleling the morphological development.
Duffy C J; Teyler T J
Brain research bulletin
1978
1978-08
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/10.1016/0361-9230(78)90097-7" target="_blank" rel="noreferrer noopener">10.1016/0361-9230(78)90097-7</a>
Development of potentiation in the dentate gyrus of rat: physiology and anatomy.
Female; Male; Animals; Rats; In Vitro Techniques; Hippocampus/anatomy & histology/growth & development/*physiology; Inbred Strains
The physiological development of potentiating processes in the rat dentate gyrus were compared to morphological development. Rapid Golgi techniques were coupled with in vitro studies of dentate granule cell frequency potentiation, post-tetanic potentiation and long-term potentiation. Frequency potentiation and long-term potentiation exhibited a developmental progression between 7 and 210 days postnatal. Posttetanic potentiation remained constant across this period. The relation of these findings to synaptogenesis and dendritic spine formation are discussed.
Duffy C J; Teyler T J
Brain research bulletin
1978
1978-10
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/10.1016/0361-9230(78)90070-9" target="_blank" rel="noreferrer noopener">10.1016/0361-9230(78)90070-9</a>
Direct microinjection of cathinone into the rat brain produces discriminative stimuli.
*Brain/anatomy & histology; Alkaloids/administration & dosage/*pharmacology; Animals; Discrimination (Psychology)/*drug effects; Discrimination Learning/drug effects; Dose-Response Relationship; Drug; Inbred Strains; Injections; Intraventricular; Male; Microinjections; Nucleus Accumbens/anatomy & histology; Psychotropic Drugs/*pharmacology; Rats
Rats were trained to discriminate IP administration of 800 micrograms/kg cathinone using a food-motivated, two-lever discrimination procedure. Following training, 800 micrograms/kg cathinone discrimination was produced (generalized) by lower cathinone doses in a dose-responsive manner after IP administration; an ED50 value of 330 micrograms/kg was calculated. Subsequently, guide cannulae were implanted into the lateral ventricle and bilaterally into the nucleus accumbens. After recovery, injections were made via cannulae that extended 0.5 mm past the tip of the guide cannulae. ICV administration of 256 micrograms cathinone/rat produced discriminative responding on the cathinone-appropriate lever to the same degree as did the peripherally administered training dose of cathinone. Decreasing ICV doses produced decreased discriminative performance and allowed the calculation of an ED50 value of 90.5 micrograms. Likewise, administration of 64 micrograms cathinone/nucleus accumbens (for a total of 128 micrograms/rat) substituted for the IP training dose of cathinone. These results evidence the central mediation of the cathinone-induced discriminative stimulus cue and show that administration of cathinone into the nucleus accumbens is sufficient to produce these stimuli. Thus, these data suggest that receptors in the nucleus accumbens are important for the discrimination of this psychostimulant.
Schechter M D; Schechter J B; Calcagnetti D J
Pharmacology, biochemistry, and behavior
1992
1992-08
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/10.1016/0091-3057(92)90007-3" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(92)90007-3</a>
Discriminative effects of cocaethylene in rats trained to discriminate cocaine or ethanol.
Animals; Cocaine/*analogs & derivatives/*pharmacology; Discrimination Learning/*drug effects; Dose-Response Relationship; Drug; Drug Interactions; Ethanol/*pharmacology; Inbred Strains; Male; Rats
Two groups of rats were trained to discriminate between the stimulus properties of either intraperitoneally administered 10.0 mg/kg cocaine or 60 mg/kg ethanol and its vehicle in a two-lever operant chamber. Once trained, both groups exhibited a dose-related decrease in discriminative performance when tested with lower doses. A dose of 10 mg/kg cocaine, as well as doses of 10-30 mg/kg cocaethylene, in the ethanol-trained animals produced no greater than 38.9% responding on the ethanol-appropriate lever. Combinations of the approximate ethanol ED50 dose with either 10 mg/kg cocaine or 20 mg/kg cocaethylene did not increase ethanol lever responding. In contrast, in the cocaine-trained animals, administration of cocaethylene produced dose-responsive cocaine-like discrimination with 30 mg/kg producing 88.9% responding on the cocaine-appropriate lever. In addition, 600 mg/kg ethanol co-administered with a (2.5 mg/kg) dose of cocaine that was poorly discriminated produced 85% of responses on the cocaine-appropriate lever. The peak effect of cocaine and cocaethylene were observed to occur in 15-30 min post-administration with cocaine choice behavior decreasing at a faster rate than seen for cocaethylene discrimination. Results are discussed in light of ethanol and cocaine producing a heightened, as well as prolonged, euphoria in humans.
Schechter M D
Life sciences
1994
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/10.1016/0024-3205(94)00638-5" target="_blank" rel="noreferrer noopener">10.1016/0024-3205(94)00638-5</a>
Discriminative stimulus control by the anxiogenic beta-carboline FG 7142: generalization to a physiological stressor.
Male; Animals; Rats; Discrimination Learning/*drug effects; Avoidance Learning/drug effects; Appetite Depressants/*pharmacology; Carbolines/*pharmacology; Stress; Inbred Strains; Generalization; Stimulus/*drug effects; Physiological/*psychology
Drug discrimination was employed to investigate the similarities between FG
Leidenheimer N J; Schechter M D
Pharmacology, biochemistry, and behavior
1988
1988-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Discriminative stimulus effect of phenylephrine.
Male; Animals; Rats; Cues; Adrenergic alpha-Antagonists/pharmacology; Discrimination (Psychology)/*drug effects; Reinforcement Schedule; Phenylephrine/*pharmacology; Adrenergic alpha-Agonists/pharmacology; Dose-Response Relationship; Drug; Inbred Strains; Receptors; Generalization; Stimulus/drug effects; Adrenergic; alpha/drug effects
Rats were trained to discriminate phenylephrine in a two-lever, food-motivated operant task by increasing the i.p. administered training dose from 0.8 to 2 mg/kg. Stable discrimination to 2 mg/kg phenylephrine was established and testing of 0.5-2.5 mg/kg was shown to be dose-responsive and allowed for a calculated ED50 value of 0.87 mg/kg. Administration of methoxamine (0.5-6 mg/kg), another alpha 1-adrenoceptor agonist, produced a dose-responsive generalization, whereas only the lowest (0.04 mg/kg) and highest (0.12 mg/kg) doses of the alpha
Schechter M D
Archives internationales de pharmacodynamie et de therapie
1991
1991-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Discriminative stimulus properties of (+)cathine, an alkaloid of the khat plant.
Male; Animals; Rats; Drug Administration Schedule; Drug Tolerance; Psychotropic Drugs/*pharmacology; Haloperidol/pharmacology; Alkaloids/*pharmacology; *Discrimination (Psychology)/drug effects; Catha; Domperidone/pharmacology; Phenylpropanolamine/antagonists & inhibitors/*pharmacology; Plant Extracts/analysis; Inbred Strains
The effects of the psychostimulant (+)cathine (norpseudoephedrine) were examined in a two-choice, food-motivated, drug-discrimination paradigm. Rats were able to discriminate cathine from vehicle and this effect was dose- and time-dependent. Prior administration of cathine resulted in a diminished response (tolerance) to subsequent cathine and this effect developed and dissipated rapidly. Thus, different dose-response curves were generated depending upon whether cathine or vehicle was administered the day before testing. The development of tolerance also shortened cathine's time course of action and enhanced the ability of haloperidol to antagonize the cathine cue. These results suggest caution in interpreting effects produced by intermittent drug injection schedules.
Pehek E A; Schechter M D
Pharmacology, biochemistry, and behavior
1990
1990-06
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/10.1016/0091-3057(90)90402-4" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(90)90402-4</a>
Discriminative stimulus properties of CGS 9896: interactions within the GABA/benzodiazepine receptor complex.
Male; Animals; Rats; Pentobarbital/pharmacology; Carbolines/pharmacology; Chlordiazepoxide/pharmacology; Discrimination (Psychology)/drug effects/*physiology; Flumazenil/pharmacology; gamma-Aminobutyric Acid/analogs & derivatives/pharmacology; Pentylenetetrazole/pharmacology; Pyrazoles/antagonists & inhibitors/*metabolism; Dose-Response Relationship; Drug; Inbred Strains; Receptors; GABA-A/*physiology
Male rats were trained to discriminate the stimulus effects of CGS 9896 (30.0 mg/kg) from its vehicle. Once trained, discriminative performance was observed to be dose-responsive in the 3.75-30.0 mg/kg range and analysis of the dose-response curve generated an ED50 of 6.44 mg/kg. Generalization testing with chlordiazepoxide and pentobarbital produced CGS 9896-appropriate responding, whereas administration of the GABA agonists SL 75 102 resulted in 75% (intermediate) generalization to the CGS 9896 discriminative stimulus. Although full antagonism of the CGS 9896 cue was obtained following administration of Ro15-1788 and pentylenetetrazole, the inverse agonist DMCM failed to provide complete antagonism. These results suggest that the discriminative properties of CGS 9896 are consistent with its activity as a benzodiazepine receptor agonist.
Leidenheimer N J; Schechter M D
Pharmacology, biochemistry, and behavior
1988
1988-10
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/10.1016/0091-3057(88)90342-5" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(88)90342-5</a>
Dopaminergic nature of acute cathine tolerance.
Male; Animals; Rats; Drug Tolerance; Dopamine/*physiology; Discrimination (Psychology)/drug effects; Discrimination Learning/drug effects; Alkaloids/pharmacology; Thiazepines/pharmacology; Antipsychotic Agents/pharmacology; Appetite Depressants/*pharmacology; Phenylpropanolamine/*pharmacology; Generalization (Psychology)/drug effects; Dose-Response Relationship; Drug; Inbred Strains
Cathine is a psychoactive constituent in the leaves of the Khat shrub which are habitually ingested for their stimulatory effects in many parts of the world. Rats were trained to discriminate the stimulus effect of intraperitoneally administered 4.8 mg/kg d-cathine and, once trained, administration of another Khat constituent, cathinone, was shown to produce cathine-like effects. This generalization to cathinone was dose-responsive when testing occurred 24 hr after vehicle administration, whereas prior administration of cathine resulted in a diminished discriminative response to subsequent cathinone administration possibly as a result of the development of acute tolerance. CGS 10746B, a compound that blocks presynaptic release of dopamine, significantly decreased rats' ability to discriminate cathine when it was administered 25 min prior to cathine testing and it reversed the acute tolerance observed when cathine was tested 24 hr after cathine administration. These results indicate that a previously reported acute tolerance effect to cathine after cathinone administration in cathinone-trained rats appears to be symmetrical in that there is acute tolerance to cathinone after cathine in these cathine-trained rats. The results with CGS 10746B would suggest that both the cathine-induced discriminative cue and cathine's ability to produce acute tolerance are mediated by presynaptic dopamine release.
Schechter M D
Pharmacology, biochemistry, and behavior
1990
1990-08
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/10.1016/0091-3057(90)90083-t" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(90)90083-t</a>
Effect of altering dopamine or serotonin neurotransmitters upon cathinone discrimination.
Alkaloids/*pharmacology; Animals; Antipsychotic Agents/pharmacology; Calcium Channel Blockers/pharmacology; Dihydropyridines/pharmacology; Discrimination (Psychology)/*drug effects; Discrimination Learning/drug effects; Dopamine/*physiology; Dose-Response Relationship; Drug; Inbred Strains; Isradipine; Male; Neurotransmitter Agents/*physiology; Psychotropic Drugs/*pharmacology; Rats; Serotonin Antagonists/pharmacology; Serotonin/*physiology; Thiazepines/pharmacology; Tropanes/pharmacology
Rats were trained to discriminate between the stimulus properties of 0.8 mg/kg l-cathinone and its vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance when tested with lower cathinone doses. An analysis of the dose-response curve indicated an ED50 value of 0.23 mg/kg. Pretreatment with CGS 10746B (5-20 mg/kg) resulted in a dose-related decrease in cathinone discrimination with the highest dose blocking cathinone discrimination. In contrast to the ability of this dopamine release inhibitor to decrease cathinone discrimination, pretreatment with three doses of the calcium channel blocker isradipine (2.5-10 mg/kg) or with the 5-HT3 antagonist MDL 72222 (0.1-0.4 mg/kg) had no effect upon cathinone discrimination. The results suggest that cathinone controls differential responding in a discriminative stimulus task by a mechanism involving presynaptic release of dopamine, which may not be regulated by either neuronal calcium influx through L-type calcium channels or by serotonergic neurons.
Schechter M D
Pharmacology, biochemistry, and behavior
1992
1992-01
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/10.1016/0091-3057(92)90055-k" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(92)90055-k</a>
Effect of learned behavior upon conditioned place preference to cathinone.
Male; Animals; Rats; Dopamine/physiology; Cues; Discrimination (Psychology)/drug effects; Discrimination Learning/drug effects; Thiazepines/pharmacology; Antipsychotic Agents/pharmacology; Alkaloids/*pharmacology; Learning/*physiology; Inbred Strains; Receptors; Conditioning; Operant/*drug effects; Dopamine/drug effects
The purpose of this study was to examine whether first training rats to discriminate the stimulus cues produced by an indirect dopamine agonist, cathinone, would influence a subsequent test of preference. The conditioned place preference (CPP) paradigm was used to evaluate the reinforcing effects of l-cathinone in four differently treated groups of rats. Half of the animals were trained to discriminate the interoceptive cues produced by 0.8 mg/kg cathinone in a two-lever, food-motivated operant task. The other animals were equally divided between two groups, one receiving saline and noncontingent reinforcements on the same schedule as those trained to discriminate cathinone; the other group, the "yoked-control" rats, received the same cathinone and saline regimen of administration as the discrimination-trained animals. Results of CPP testing indicate that cathinone produced a statistically significant conditioned place preference only in the group trained to discriminate cathinone and not in the saline or yoked control groups. Furthermore, when half of the cathinone discrimination-trained rats were pretreated with the dopamine release inhibitor CGS 10746B, the conditioned place preference to cathinone was attenuated. The results would indicate that pairing cathinone with a nonpreferred environment tended to make the rat spend more time in that environment and the amount of time spent in the cathinone-associated environment can be increased by prior discrimination training and decreased by diminished dopamine function in the brain.
Schechter M D
Pharmacology, biochemistry, and behavior
1991
1991-01
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/10.1016/0091-3057(91)90582-m" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(91)90582-m</a>
Effect of MDMA neurotoxicity upon its conditioned place preference and discrimination.
Male; Animals; Rats; Discrimination Learning/*drug effects; Choice Behavior/*drug effects; Designer Drugs/*toxicity; Nervous System/*drug effects; Sodium Chloride/pharmacology; Dose-Response Relationship; Drug; Inbred Strains; 3; Conditioning; Classical/*drug effects; N-Methyl-3; 4-methylenedioxyamphetamine; 4-Methylenedioxyamphetamine/*analogs & derivatives/toxicity
Experiments were conducted to investigate the functional consequences of a neurotoxic regimen of MDMA administration upon two behaviors, conditioned place preference and drug discrimination. Rats were trained to discriminate 1.5 mg/kg MDMA from its vehicle and their discriminative performance was shown to be dose-responsive. Subsequently, MDMA was observed to produce a conditioned place preference as three conditioning sessions with 1.5 mg/kg MDMA paired with the nonpreferred chamber increased the time the rats spent in the chamber paired with MDMA. Administration of a proportedly neurotoxic dose (20 mg/kg subcutaneous) of MDMA, twice-a-day for four days, did not affect this conditioned place preference when it was redetermined at a time of maximal neurochemical compromise. In contrast, sensitivity to 1.0 mg/kg MDMA in the drug discrimination task was shown to be significantly decreased after the neurotoxic regimen. Results are discussed in light of MDMA effects upon both central serotonergic and dopaminergic neurons.
Schechter M D
Pharmacology, biochemistry, and behavior
1991
1991-03
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/10.1016/0091-3057(91)90010-y" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(91)90010-y</a>
Effect of repeated administrations upon cathinone discrimination and conditioned place preference.
Male; Animals; Rats; Psychotropic Drugs/*pharmacology; Discrimination (Psychology)/*drug effects; Alkaloids/*pharmacology; Drug Tolerance/physiology; Inbred Strains; Conditioning; Operant/*drug effects
1. Eight male rats were trained to discriminate the interoceptive cues produced by 0.8 mg/kg l-cathinone in a two-lever, food-motivated operant task and they were, subsequently, tested for preference to cathinone in a conditioned place preference (CPP)-test. 2. Once trained, the rats were placed on a 10 day regimen of twice-a-day non-contingent administrations of saline followed by a similar regimen of multiple injections of 0.8 mg/kg cathinone. 3. After each series of non-contingent administrations, the rats' ability to discriminate (0.2-0.8 mg/kg) cathinone, as well as their preference for it, was determined. 4. Results indicate that tolerance tends to develop to the effect of cathinone in its ability to control discriminative behavior as indicated by deficits in discriminative performance and a two-fold shift of the dose-response curve to the right. 5. In contrast, preference for cathinone, in the CPP-tests, was not significantly affected by the multiple cathinone administration regimen. 6. The possibility that tolerance to some behavioral effects may occur in habitual users of the cathinone-containing Khat shrub is discussed.
Schechter M D; McBurney D
General pharmacology
1991
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/10.1016/0306-3623(91)90204-j" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(91)90204-j</a>
Effect of serotonin depletion by p-chlorophenylalanine upon discriminative behaviours.
Male; Animals; Rats; Dopamine/physiology; Brain Chemistry/drug effects; Central Nervous System Stimulants/pharmacology; Discrimination (Psychology)/*drug effects; Serotonin/*physiology; Fenclonine/*pharmacology; Serotonin Antagonists/*pharmacology; Inbred Strains
1. Para-chlorophenylalanine (p-CPA), a competitive inhibitor of the serotonin (5-HT) synthesis enzyme tryptophan hydroxylase, was administered to rats at a dosage (100 mg/kg daily for 3 days) that depletes 5-HT. 2. Different groups of these rats were previously trained to discriminate the interoceptive stimuli produced by amphetamine, cathinone, 3,4-methylenedioxymethamphetamine (MDMA),
Schechter M D
General pharmacology
1991
1905-6
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/10.1016/0306-3623(91)90226-v" target="_blank" rel="noreferrer noopener">10.1016/0306-3623(91)90226-v</a>
Effects of cathinone and amphetamine on the neurochemistry of dopamine in vivo.
Male; Animals; Rats; Molecular Structure; Structure-Activity Relationship; Reference Values; Kinetics; Dopamine/*metabolism; Brain/drug effects/*metabolism; Psychotropic Drugs/*pharmacology; Alkaloids/*pharmacology; Amphetamine/*pharmacology; Caudate Nucleus/metabolism; Homovanillic Acid/metabolism; Nucleus Accumbens/metabolism; Putamen/metabolism; Inbred Strains; 3; 4-Dihydroxyphenylacetic Acid/metabolism
The effects of (-)cathinone, the primary psychoactive alkaloid of the Khat plant, were compared to those of (+)amphetamine in the anterior caudate-putamen and the nucleus accumbens. In vivo microdialysis was used to measure extracellular levels of dopamine and metabolites in both regions of the brain simultaneously, after intraperitoneal administration of 0.8, 1.6 or 3.2 mg/kg of either drug (doses expressed as the salts). Both drugs increased levels of dopamine but decreased levels of metabolites in a dose-dependent manner. However, the relative magnitude of these effects depended upon the specific drug, the dose and area of the brain examined. At the largest dose used, amphetamine had a relatively greater effect than cathinone on dopamine in both caudate and accumbens. However, among smaller doses, this difference was only observed in the nucleus accumbens after administration of 1.6 mg/kg. The results also demonstrated a differential regional effect of both drugs at 3.2 mg/kg, in that both had a greater effect on dopamine in the caudate, as opposed to the accumbens. These findings demonstrate a functional heterogeneity of the striatum of the rat, that may be relevant to the understanding of both normal brain function and the neural responses to psychoactive drugs.
Pehek E A; Schechter M D; Yamamoto B K
Neuropharmacology
1990
1990-12
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/10.1016/0028-3908(90)90041-o" target="_blank" rel="noreferrer noopener">10.1016/0028-3908(90)90041-o</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>
Extinction of cocaine-induced place approach in rats: a validation of the "biased" conditioning procedure.
Animals; Classical; Cocaine/*pharmacology; Conditioning; Extinction; Habituation; Inbred Strains; Male; Operant/*drug effects; Psychological/*drug effects; Psychophysiologic/drug effects; Rats; Reward
It has often been demonstrated that when a rat is conditioned in a cue-specific environment that has been repeatedly paired with cocaine injections, it will spend more time in that environment than it does in a saline-paired environment. This behavioral procedure is commonly known as the conditioned place preference (CPP)-test. At present, a firm theoretical understanding of the mechanisms underlying the production of a CPP are unknown. It is insufficient merely to know that a CPP can result after repeated drug pairings. Rather, it is necessary that the procedure is validated within a learning theory framework. The objective of the present study was, therefore, to establish that what is observed in place preference studies was, indeed, conditioning. This was accomplished by determining whether a cocaine-induced increase in time spent in a drug-paired environment was subject to attenuation following extinction trials. Rats were tested for their initial bias in spending more time in one of two stimulus-specific chambers of a place-conditioning apparatus. On four occasions, rats were injected with 2.5 mg/kg cocaine and confined to their less-preferred chamber whereas, on four alternating sessions, they were conditioned with saline (vehicle) in their preferred chamber. Subsequent testing in the nondrugged state revealed that these rats displayed a significant increase in the time spent in their initially least-preferred environment compared to baseline measurements. Following establishment of this cocaine-induced CPP, the rats were injected only with saline and conditioned for an equal number of sessions (i.e., four).(ABSTRACT TRUNCATED AT 250 WORDS)
Calcagnetti D J; Schechter M D
Brain research bulletin
1993
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/10.1016/0361-9230(93)90102-h" target="_blank" rel="noreferrer noopener">10.1016/0361-9230(93)90102-h</a>
Functional consequences of fenfluramine neurotoxicity.
Male; Animals; Rats; Discrimination Learning/drug effects; Reinforcement Schedule; Fenfluramine/*toxicity; Nervous System Diseases/*chemically induced/psychology; Dose-Response Relationship; Drug; Inbred Strains; Conditioning; Operant/drug effects
Male Sprague-Dawley rats were trained to discriminate the anorectic drug d,l-fenfluramine (2.0 mg/kg intraperitoneally administered) from its vehicle using a food-motivated (fixed-ratio 10 schedule) two-lever operant task. Once trained, doses of 0.5, 1.0 and 1.5 mg/kg fenfluramine tested 20 min after IP administration produced dose-responsive discrimination performance. Subsequently, noncontingent twice-a-day administrations of 1 ml/kg saline were made for 4 days and the dose-effect relationship redetermined on the 13th to 15th day after initiation of the chronic saline regimen. Results of these dose-response experiments indicated that there was no significant effect upon fenfluramine discrimination after multiple saline injections or after 10 days without training. Following four days of retraining, 6.25 mg/kg fenfluramine twice-a-day for four days was followed 10 days later by another dose-response determination. This purportedly neurotoxic regimen of fenfluramine significantly increased the rats' ability to discriminate fenfluramine. These results suggest the possibility that chronic release of serotonin or selective damage to serotonin-containing neurons produced by fenfluramine may lead to postsynaptic supersensitivity as manifested by the functionally increased discriminative performance observed.
Schechter M D
Pharmacology, biochemistry, and behavior
1990
1990-12
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<a href="http://doi.org/10.1016/0091-3057(90)90536-q" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(90)90536-q</a>