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.
Boyce-Rustay
Janel M
JM
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland, USA. janel.boyce-rustay@abbott.com
Wiedholz
Lisa M
LM
Millstein
Rachel A
RA
Carroll
Jenna
J
Murphy
Dennis L
DL
Daws
Lynette C
LC
Holmes
Andrew
A
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002940:Circadian Rhythm; D003216:Conditioning, Operant / Q000187:drug effects; D003863:Depression / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D007035:Hypothermia / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012201:Reward; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D002492:Central Nervous System Depressants; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D000431:Ethanol