SEQUENCING THE NEUROPEPTIDE Y GENE IN THE RHESUS MACAQUE (MACACA MULATTA) AND ITS ASSOCIATION WITH ALCOHOL CONSUMPTION

Abstract

Neuropeptide Y (NPY) is an anxiolytic peptide that is involved in modulation of stress response. Dysregulation of the NPY system and NPY replacement have been associated with alterations in alcohol intake in both animals and humans. The rhesus NPY gene was sequenced to screen for functional genetic variants in the rhNPY gene/promoter. Twelve polymorphisms were identified in the 5'flanking and coding regions of the rhNPY gene. One of these (-1002T>G) disrupts a putative androgen/glucocorticoid response element site. Consistent with the demonstrated role for androgens in induction of NPY, carriers the -1002 G allele exhibited lower levels of NPY in cerebrospinal fluid as well as appeared to be sensitized behaviorally to a stressful paradigm. This NPY promoter variant was also associated with increased alcohol intake in animals without a history of dependence, with the effect being more marked among animals exposed to early adversity in the form of peer rearing.