Abstract # 2068 Event # 133:

Scheduled for Friday, August 18, 2006 05:30 PM-05:50 PM: Session 13 (Regency East #1) Oral Presentation


POLYMORPHISMS IN STRESS PATHWAY GENES THAT INFLUENCE ALCOHOL CONSUMPTION IN STRESS- AND ALCOHOL-EXPOSED RHESUS MACAQUES (Macaca mulatta): EVIDENCE FOR AN ALLOSTATIC SHIFT?

C. S. Barr1,2, M. Gupte1, T. K. Newman1, S. G. Lindell1, S. J. Suomi2, D. Goldman1 and J. D. Higley1
1NIH/NIAAA, Poolesville, MD 20837, USA, 2NIH/NICHD
line
     Corticotropin Releasing Hormone and Neuropeptide Y are opposing neuropeptides critically involved in stress responding. There is evidence from rodent studies that perturbation of the CRH and NPY systems also underlie transition to the addicted state. We have identified functional variants in the regulatory regions for the rhesus macaque CRH and NPY genes, both of which increase endocrine and behavioral responses to stress. We wanted to determine whether they would also be associated with individual differences in alcohol consumption. Animals were given simultaneous access to an aspartame-sweetened 8.4% v/v ethanol solution and vehicle for 1 h/day, 5 days/week, and the effects of rhCRH and rhNPY polymorphisms on alcohol consumption were determined by ANOVA. Alcohol consumption was higher among rhCRHA2 carriers. Moreover, there was an interaction between genotype and ethanol exposure; An escalation in ethanol consumption was observed among carriers of the rhCRHA2 allele, but not among A1 homozygotes. Variation in the rhNPY promoter was also associated with alcohol consumption, but only among peer-reared animals homozygous for the minor allele. These data demonstrate rhCRH and rhNPY gene variants to be associated with increased alcohol consumption in rhesus, but only as a function of exposures to alcohol or early life stress. These studies suggest a role for neuropeptide gene variation in the susceptibility to alcohol-related disorders and further implicate these systems as treatment targets in selected individuals.