Effect of repeated abstinence on chronic ethanol self-administration in the rhesus monkey

Daicia C. Allen, Steven W. Gonzales, Kathleen A. Grant

Abstinence-based approaches to treating alcohol use disorder (AUD) are highly prevalent, but abstinence from chronic drinking may exacerbate subsequent levels of alcohol intake in relapse. Use a non-human primate model that encompasses a range of chronic voluntary ethanol drinking to isolate biological responses to repeated cycles of imposed abstinence as a function of baseline voluntary alcohol drinking levels. Over a 26-month protocol, young adult male rhesus macaques were first induced to drink alcohol and then given continuous access to 4% (w/v) ethanol (n = 8) or water (n = 4) for approximately 14 months, followed by three 28- to 35-day abstinence phases, with 3 months of ethanol access in between. Ethanol intake and blood ethanol concentration (BEC) were the primary dependent variables. Observational signs of physical dependence and circulating ACTH and cortisol were monitored. Prior to abstinence, stable, categorical, individual differences in voluntary ethanol intake under chronic access conditions were found. Following abstinence, categorical "non-heavy" drinking subjects increased drinking transiently (increased between 0.7 and 1.4 g/kg/day in first month after abstinence) but returned to baseline after 3 months. Categorical "heavy" drinkers, however, maintained drinking 1.0-2.6 g/kg above baseline for over 3 months following abstinence. Signs of physical dependence were rare, although huddling and social withdrawal increased in ethanol and control subjects. The most prominent effect on hormonal measures was heightened cortisol during abstinence that increased to a greater extent in ethanol subjects. Involuntary abstinence increases drinking in the absence of overt physical withdrawal symptoms, and heavy drinkers are more robustly affected compared to non-heavy drinkers.