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Deletion of the 5-HT(3A)-receptor subunit blunts the induction of cocaine sensitization

Hodge, Clyde W., Bratt, Alison M., Kelley, Stephen P. (2008) Deletion of the 5-HT(3A)-receptor subunit blunts the induction of cocaine sensitization. Genes Brain and Behavior, 7 (1). pp. 96-102. ISSN 1601-1848. (doi:10.1111/j.1601-183X.2007.00332.x) (KAR id:11374)


Serotonin (5-HT) receptors are classified into seven groups (5-HT1–7), comprising at least 14 structurally and pharmacologically distinct receptor subtypes. Pharma-cological antagonism of ionotropic 5-HT3 receptors has been shown to modulate both behavioral and neuro-chemical aspects of the induction of sensitization to cocaine. It is not known, however, if specific molecular subunits of the 5-HT3 receptor influence the development of cocaine sensitization. To address this question, we studied the effects of acute and chronic intermittent cocaine administration in mice with a targeted deletion of the gene for the 5-HT3A-receptor subunit (5-HT3A ?/?). 5-HT3A (?/?) mice showed blunted induction of cocaine-induced locomotor sensitization as compared with wild-type littermate controls. 5-HT3A (?/?) mice did not differ from wild-type littermate controls on measures of basal motor activity or response to acute cocaine treatment. Enhanced locomotor response to saline injection following cocaine sensitization was observed equally in 5-HT3A (?/?) and wild-type mice suggesting similar conditioned effects associated with chronic cocaine treatment. These data show a role for the 5-HT3A-receptor subunit in the induction of behavioral sensitization to cocaine and suggest that the 5-HT3A molecular subunit modulates neurobehavioral adaptations to cocaine, which may underlie aspects of addiction.

Item Type: Article
DOI/Identification number: 10.1111/j.1601-183X.2007.00332.x
Uncontrolled keywords: 5-HT3, 5-HT3A-receptor subunit, cocaine, conditioning, environment, locomotion, sensitization
Subjects: Q Science > QP Physiology (Living systems)
R Medicine > RM Therapeutics. Pharmacology
Q Science > QH Natural history > QH426 Genetics
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Alison Kelley
Date Deposited: 29 Jun 2011 17:04 UTC
Last Modified: 16 Nov 2021 09:50 UTC
Resource URI: (The current URI for this page, for reference purposes)

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Bratt, Alison M..

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Kelley, Stephen P..

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