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Christina S. Barr, VMD, PhD; Timothy K. Newman, PhD; Stephen Lindell, BA; Courtney Shannon, BA; Maribeth Champoux, PhD; Klaus Peter Lesch, MD; Stephen J. Suomi, PhD; David Goldman, MD; J. Dee Higley, PhD

Arch Gen Psychiatry. 2004;61:1146-1152.

Background  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.

Methods  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.

Results  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.

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

Author Affiliations: National Institute on Alcoholism and Alcohol Abuse, Laboratory of Clinical Studies (Drs Barr, Newman, and Higley and Mr Lindell) and National Institute of Child Health and Human Development, Laboratory of Comparative Ethology (Drs Champoux and Suomi and Ms Shannon), National Institutes of Health, Poolesville, Md; Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany (Dr Lesch); and National Institute on Alcoholism and Alcohol Abuse, Laboratory of Neurogenetics, Rockville, Md (Dr Goldman).

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