Open AccessDeletion of the 5‐HT 3A ‐receptor subunit blunts the induction of cocaine sensitization
Author(s) -
Hodge C. W.,
Bratt A. M.,
Kelley S. P.
Publication year - 2008
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/j.1601-183x.2007.00332.x
Subject(s) - sensitization , neurochemical , 5 ht receptor , receptor , serotonin , ionotropic effect , pharmacology , protein subunit , agonist , medicine , endocrinology , biology , chemistry , neuroscience , glutamate receptor , biochemistry , gene
Serotonin (5‐HT) receptors are classified into seven groups (5‐HT 1–7 ), comprising at least 14 structurally and pharmacologically distinct receptor subtypes. Pharmacological antagonism of ionotropic 5‐HT 3 receptors has been shown to modulate both behavioral and neurochemical aspects of the induction of sensitization to cocaine. It is not known, however, if specific molecular subunits of the 5‐HT 3 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‐HT 3A ‐receptor subunit (5‐HT 3A −/−). 5‐HT 3A (−/−) mice showed blunted induction of cocaine‐induced locomotor sensitization as compared with wild‐type littermate controls. 5‐HT 3A (−/−) 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‐HT 3A (−/−) and wild‐type mice suggesting similar conditioned effects associated with chronic cocaine treatment. These data show a role for the 5‐HT 3A ‐receptor subunit in the induction of behavioral sensitization to cocaine and suggest that the 5‐HT 3A molecular subunit modulates neurobehavioral adaptations to cocaine, which may underlie aspects of addiction.