Conditioned place preference for cocaine is attenuated in mice over-expressing the 5-HT3 receptor

The serotonin 5-HT3 receptor is thought to play a role in the reward pathway and drug abuse by modulating dopamine release within the mesolimbic pathway. Dopamine release stimulated by cocaine and methamphetamine is blocked by administration of 5-HT3 receptor antagonists. Animal studies demonstrate...

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Bibliographic Details
Published in:Psychopharmacologia 2001-10, Vol.158 (1), p.18-27
Main Authors: ALLAN, A. M, GALINDO, R, CHYNOWETH, J, ENGEL, S. R, SAVAGE, D. D
Format: Article
Language:English
Subjects:
Anatomical correlates of behavior
Behavioral psychophysiology
Biological and medical sciences
Brain slice preparation
Cocaine
Dopamine
Dopamine D1 receptors
Dopamine D2 receptors
Dopamine D3 receptors
Dopamine D4 receptors
Dopamine transporter
Drug abuse
Drug addictions
Forebrain
Fundamental and applied biological sciences. Psychology
Medical sciences
Mesolimbic system
Methamphetamine
Overexpression
Place preference conditioning
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Serotonin S3 receptors
Toxicology
Transgenic mice
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Summary:The serotonin 5-HT3 receptor is thought to play a role in the reward pathway and drug abuse by modulating dopamine release within the mesolimbic pathway. Dopamine release stimulated by cocaine and methamphetamine is blocked by administration of 5-HT3 receptor antagonists. Animal studies demonstrate that 5-HT3 receptor antagonists decrease cocaine and methamphetamine preference. We have developed a 5-HT3 receptor over-expressing mouse to study the role of this receptor in substance abuse. No changes in either the dopamine receptors (D1, D2, D3, and D4) or in the dopamine transporter (DAT) were found over a wide range of brain regions. 5-HT3 receptor over-expressing mice failed to develop conditioned place preference to 10 mg/kg or 6 mg/kg cocaine but showed a modest preference for 4 mg/kg cocaine. 5HT3 receptor over-expressing mice were more sensitive to the locomotor activating effects of low dose cocaine and methamphetamine. Further, brain slices from the transgenic mice release more dopamine in response to low concentrations of cocaine. These data suggest that 5HT3 receptor over-expression in the forebrain decreases cocaine preference and increases acute sensitivity with a corresponding increase in the amount of dopamine released in response to cocaine.
ISSN:0033-3158
1432-2072
DOI:10.1007/s002130100833