Abstract # 162:

Scheduled for Friday, August 19, 2005 07:00 PM-09:00 PM: (Cambridge/Oxford Room) Poster Presentation


ASSOCIATION OF A CORTICOTROPIN-RELEASING HORMONE (CRH) GENE HAPLOTYPE WITH ALCOHOL-INDUCED STRESS AXIS ACTIVITY IN RHESUS MACAQUES (Macaca mulatta)

M. McKee1,2, C. S. Barr1,2, R. L. Dvoskin1,2, S. Higley1, T. K. Newman1,2, S. J. Suomi3, D. Goldman2 and J. D. Higley1
1LCTS/NIAAA/NIH, NIH Animal Center, PO Box 529, Poolesville, MD 20837, 2LNG/NIAAA/NIH, 3LCE/NICHD/NIH
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     Corticotropin-releasing hormone (CRH) is the primary neuropeptide responsible for activation of the hypothalamic-pituitary-adrenal (HPA) axis, and perturbation of both the CRH system and the HPA axis are associated with certain neuropsychiatric disorders in addition to alcohol use and withdrawal. As such, the CRH gene may be a good candidate for investigating genetic variation as it relates to vulnerability to anxiety and mood disorders, neuroendocrine stress axis dysregulation, and alcoholism. We have identified a number of polymorphisms within the 5’flanking and coding regions for the CRH gene in rhesus macaques (rhCRH). One haplotype cluster (rhCRH-A2) is present in 15% of the animals in our colony. We wanted to determine whether the rhCRH-A2 haplotype cluster would be associated with increased HPA axis activity in response to alcohol. At approximately 4 years of age, animals (N = 90) received an intravenous infusion of alcohol (2-2.2 g/kg); ACTH and cortisol levels were determined at baseline and following alcohol infusion. Effects of rhCRH gene variation on HPA axis output were analyzed using repeated measures ANOVA. The rhCRH-A2 haplotype cluster was associated with increased ACTH (P < 0.01) and cortisol (P < 0.05) levels following alcohol. These data demonstrate that rhCRH gene variation is associated with increased HPA activity in response to alcohol in rhesus macaques and may suggest a role for human CRH gene variation in susceptibility to alcohol-related disorders.