Abstract
BACKGROUND: Clinical and preclinical alcohol use disorder (AUD) research demonstrates that males and females differ in motivations behind drinking, patterns of drinking behaviors, and alcohol-related physiological responses and health consequences. Nonhuman primate (NHP) models of AUD have the potential to enhance our understanding of such sex differences. In NHP models, schedule-induced polydipsia is a common method to initiate ethanol drinking. In males, characteristics of drinking during the final stage of induction, when monkeys consume 1.5 g/kg/day, predict subsequent drinking patterns when monkeys have unlimited access to ethanol. The present study assessed sex differences in those predictive behaviors during induction and characterized patterns and intakes during 6 months of ethanol drinking. METHODS: Eleven singly housed adult cynomolgus monkeys (six male, five female) were induced to consume water, then increasing doses of ethanol for 4 weeks per dose (0.5, 1.0, and 1.5 g/kg) using a 300-s fixed-time schedule of food pellet delivery. Following induction, monkeys switched to an "open-access" regimen wherein water and ethanol were available 22 h/day, 5 days/week. RESULTS: Predictive relationships between drinking characteristics during the final phase of induction and subsequent open-access drinking were replicated, with no evidence of sex differences. Although weekly and total ethanol intakes were higher in males over 6 months of open access, the difference did not reach statistical significance. However, there were sex differences in the distribution of ethanol intake across the day. Males drank significantly more when meals were available, whereas females spread their drinking throughout the first half of the session; these differences were exacerbated in Month 2 and remained for the duration of the study. CONCLUSIONS: These results replicate previous findings of a predictive relationship between drinking variables during induction and later open-access drinking and reveal sex differences in daily patterns of ethanol intake that may inform treatment approaches.