Ethanol-related behaviors in serotonin transporter knockout mice

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.