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Ethanol‐Related Behaviors in Serotonin Transporter Knockout Mice
Author(s) -
BoyceRustay Janel M.,
Wiedholz Lisa M.,
Millstein Rachel A.,
Carroll Jenna,
Murphy Dennis L.,
Daws Lynette C.,
Holmes Andrew
Publication year - 2006
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2006.00241.x
Subject(s) - knockout mouse , serotonin transporter , behavioural despair test , pharmacology , psychology , transporter , gene knockout , serotonin , medicine , neuroscience , endocrinology , chemistry , antidepressant , biochemistry , hippocampus , receptor , gene
Background: Increasing evidence supports a role for 5‐hydroxytryptamine (5‐HT) and the 5‐HT transporter (5‐HTT) in modulating the neural and behavioral actions of ethanol (EtOH) and other drugs of abuse. Methods: We used a 5‐HTT knockout (KO) mouse model to further study this relationship. 5‐Hydroxytryptamine transporter KO mice were tested for the sedative/hypnotic, hypothermia‐inducing, motor‐incoordinating (via accelerating rotarod), and depression‐related (via tail suspension test) effects of acute EtOH administration. Reward‐related effects of EtOH were assessed in 5‐HTT KO mice using the conditioned place preference (CPP) paradigm. 5‐Hydroxytryptamine transporter KO mice were tested for voluntary consumption of EtOH in a modified 2‐bottle choice test that measured the temporal organization of drinking over the circadian cycle via “lickometers.” Results: Replicating previous findings, 5‐HTT KO mice exhibited significantly increased sensitivity to EtOH‐induced sedation/hypnosis relative to wild‐type controls. Additionally, 5‐HTT KO mice showed motor‐coordination deficits at baseline and in response to EtOH. Hypothermic, pro‐depressive–like, and reward‐related effects of EtOH were no different across genotypes. Gross EtOH consumption was modestly reduced in 5‐HTT KO mice, due to significantly lesser consumption during the peak period of drinking in the early dark phase. Conclusions: Data extend the finding that loss of 5‐HTT gene function alters certain neural and behavioral effects of EtOH, with implications for better understanding the pathophysiology and treatment of alcoholism.