GR38032F, a serotonin 5-HT3 antagonist, fails to alter cocaine self-administration in rats
Pharmacology Biochemistry and BehaviorPublished 1 May 1991
Rachel Peltier, Susan Schenk
Citations76
SJR quartileQ1
SJR score0.95
SNIP0.81
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The effects of the 5-HT3 antagonist, GR38032F, with the dopamine D2 receptor blocker, haloperidol, on the intravenous self-administration of cocaine in rats fail to support a role for the serotonin 5- HT3 receptor system in the reinforcing properties of this psychostimulant.
Abstract
Recent data have supported a role for serotonin (5-HT) in the self-administration of cocaine by laboratory rats. More specifically, it has been suggested that 5-HT3 receptor antagonists may be useful in the treatment of drug abuse. To assess this possibility, we compared the effects of the 5-HT3 antagonist, GR38032F, with the dopamine D2 receptor blocker, haloperidol, on the intravenous self-administration of cocaine (0.5 mg/kg/infusion) in rats. The serotonin antagonist (0.01, 0.1 or 1.0 mg/kg, IP) failed to alter self-administration (0.5 mg/kg/infusion). In contrast, haloperidol (0.125 mg/kg, IP) increased responding for cocaine (0.5 mg/kg/infusion), and shifted the dose-response curve for cocaine self-administration to the right. These data fail to support a role for the serotonin 5-HT3 receptor system in the reinforcing properties of this psychostimulant. Rather, the 5-HT1 or 5-HT2 receptors may be the critical subtype.
Keywords
PsychologyMedicineNeuroscience
Psychological ReviewA psychomotor stimulant theory of addiction.
2,700 Citations1987Roy A. Wise, Michael A. Bozarth
A new attempt at a general theory of addiction is offered, based on the common denominator of the psychomotor stimulants---amphetamine, cocaine, and related drugs---rather than on thecommon denominators of the socalled depressant drugs~opiates, barbiturates, alcohol, and others.
NeuropharmacologyProposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine
1,260 Citations1986Philip Bradley, G. Engel +7 more
This classification of 5-HT receptors into three main groups is based largely, but not exclusively, on data from studies in isolated peripheral tissues where definitive classification is possible, and is believed that this working classification will be relevant to functional responses to 5- HT in the central nervous system.
NatureIdentification and distribution of 5-HT3 receptors in rat brain using radioligand binding
866 Citations1987Gavin J. Kilpatrick, Brian Jones +1 more
Direct evidence for the existence of 5-HT3 receptors in rat brain tissue and their distribution is reported, based on high affinity binding of the potent 5- HT3 receptor antagonist 3H-GR65630 to homogenates of rat entorhinal cortex.
British Journal of Pharmacology and ChemotherapyTWO KINDS OF TRYPTAMINE RECEPTOR
843 Citations1957J. H. Gaddum, Zuleika P. Picarelli
British Journal of PharmacologyEffects of the 5‐HT<sub>3</sub> receptor antagonist, GR38032F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain
356 Citations1987B. Costall, A.M. Domeney +2 more
It is concluded that the 5‐HT3 receptor antagonist GR38032F, and the neuroleptic agents fluphenazine, sulpiride and haloperidol, can reduce raised mesolimbic dopaminergic activity in the rat and marmoset.
British Journal of PharmacologyThe potential anxiolytic activity of GR38032F, a 5‐HT<sub>3</sub>‐receptor antagonist
328 Citations1988Brian J. Jones, B. Costall +5 more
It is concluded that GR38032F is potentially a very potent anxiolytic agent without sedative, anticonvulsant or hypnotic activity.
European Journal of PharmacologyDifferential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release
275 Citations1989Ezio Carboni, Elio Acquas +2 more
The results indicate that blockade of 5-HT3 receptors selectively prevents the stimulation of DA release induced by drugs known to stimulate the firing activity of DA neurons.
Pharmacology Biochemistry and BehaviorFluoxetine reduces intravenous cocaine self-administration in rats
256 Citations1990Marilyn E. Carroll, Sylvie T. Lac +2 more
Rats self-administered intravenously delivered cocaine under a fixed-ratio (FR) 4 schedule during 24-hr sessions and behavior maintained by the G + S solution was reduced by the two higher fluoxetine doses; however, this reduction did not reliably occur until the last two days of fluoxettine administration.
Journal of Pharmacology and Experimental TherapeuticsRelease of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum.
241 Citations1989Patrizio Blandina, Joseph Goldfarb +2 more
Direct, unambiguous evidence is provided that in rat striatum 5-HT3 receptors modulate release of endogenous dopamine from superfused rat striatal slices.
PsychopharmacologyBreak-points on a progressive ratio schedule reinforced by intravenous cocaine increase following depletion of forebrain serotonin
229 Citations1990Elliot A. Loh, David C. S. Roberts
Data indicate that depletion of forebrain serotonin increases the incentive value of cocaine, and bilateral injections of 5,7-DHT into either the medial forebrain bundle (MFB) or amygdala (AMY) significantly increased the breaking points on the PR schedule compared to vehicle-injected control animals.
European Journal of PharmacologyActivation of a 5-HT3 receptor releases dopamine from rat striatal slice
161 Citations1988Patrizio Blandina, Joseph Goldfarb +1 more
Brain ResearchThe effect of intraventricular administration of the 5-HT3 receptor agonist 2-methylserotonin on the release of dopamine in the nucleus accumbens: an in vivo chronocoulometric study
159 Citations1990Lian Jiang, Charles R. Ashby +2 more
The results suggest that the 2-Me-5HT-induced DA release in the NAc is mediated by 5-HT3 receptors and is dependent upon the impulse flow of DA cells.
PsychopharmacologyAtypical neuroleptics increase self-administration of cocaine: An evaluation of a behavioural screen for antipsychotic activity
149 Citations1983David C. S. Roberts, Gary Vickers
Sulpiride, metoclopramide and thioridazine produced a dose-dependent increase in cocaine intake similar to that found for chlorpromazine, haloperidol, pimozide and flupenthixol; Clozapine, however, produced adose-dependent decrease in cocaine Intake.
PsychopharmacologyIntravenous cocaine self-administration in rats is reduced by dietaryl-tryptophan
125 Citations1990Marilyn E. Carroll, Sylvie T. Lac +2 more
The results of this experiment indicate that l-tryptophan reduces behavior reinforced by IV cocaine infusions, and behavior maintained by the highest cocaine dose was resistant to the effect ofl-t Kryptophan.
European Journal of PharmacologyEffect of the 5-HT3 receptor antagonist, GR38032F, on responses to injection of a neurokinin agonist into the ventral tegmental area of the rat brain
114 Citations1987Russell M. Hagan, A. W. Butler +4 more
Behavior Research Methods, Instruments, & ComputersParallel processing strategies in the application of microcomputers to the behavioral laboratory
108 Citations1985David Spencer, M. W. Emmett‐Oglesby
Assembly language algorithms that were found to facilitate speed of processing and flexibility of control in the Operant Package for the Neurosciences are described.