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Arch Gen Psychiatry. 2004 Nov;61(11):1146-52.

Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates.

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National Institute on Alcoholism and Alcohol Abuse, Laboratory of Clinical Studies and National Institute of Child Health and Human Development, Laboratory of Comparative Ethology, National Institutes of Health, Poolesville, MD, USA.



Serotonin neurotransmission and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hormones are thought to be involved in the reinforcement of alcohol intake and contribute to the risk for alcoholism. In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety and altered LHPA-axis responses to stress, and in female macaques, exposure to early-life stress alters LHPA-axis activation in response to alcohol. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence alcohol preference in female rhesus macaques. Because of the involvement of stress and LHPA-axis activity in symptoms of withdrawal and relapse, we also wanted to determine whether serotonin transporter gene variation and rearing condition would influence changes in the patterns of alcohol consumption across a 6-week alcohol consumption paradigm.


Female macaques were reared with their mothers in social groups (n = 18) or in peer-only groups (n = 14). As young adults, they were given access to an aspartame-sweetened 8.4% alcohol solution and vehicle for 1 hour per day, and volumes of consumption of alcoholic and nonalcoholic solutions were recorded. Serotonin transporter genotype (l/l and l/s) was determined using polymerase chain reaction followed by gel electrophoresis.


We found interactions between rearing condition and serotonin transporter genotype, such that l/s peer-reared females demonstrated higher levels of ethanol preference. We also found an effect of rearing condition on the percentage change in alcohol consumed during the 6 weeks as well as a phase by rearing interaction, such that peer-reared animals progressively increased their levels of consumption across the course of the study. This was especially evident for peer-reared females with the l/s rh5-HTTLPR genotype.


These data suggest a potential interaction between serotonin transporter gene variation and early experience in vulnerability to alcoholism.

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