Chronic Alcohol Self‐Administration in Monkeys Shows Long‐Term Quantity/Frequency Categorical Stability

Abstract

Background The current criteria for alcohol use disorders (AUD) do not include consumption (quantity/frequency) measures of alcohol intake, in part due to the difficulty of these measures in humans. Animal models of ethanol self-administration have been fundamental in advancing our understanding of the neurobiological basis of (AUD) and can address quantity/frequency measures with accurate measurements over prolonged periods of time. The non-human primate (NHP) model of voluntary oral alcohol self-administration has documented both binge drinking and drinking to dependence and can be used to test the stability of consumption measures over time. Methods and Results Here, an extensive set of alcohol intakes (g/kg/day) was analyzed from a large multi-cohort population of Rhesus (Macaca mulatta) monkeys (n=31). Daily ethanol intake was uniformly distributed over chronic (12 months) access for all animals. Underlying this distribution of intakes were subpopulations of monkeys that exhibited distinctive clustering of drinking patterns, allowing us to categorically define very heavy drinking (VHD), heavy drinking (HD), binge drinking (BD), and low drinking (LD). These categories were stable across the 12-month assessed by the protocol, but exhibited fluctuations when examined at shorter intervals. Conclusions The establishment of persistent drinking categories based on quantity/frequency suggests that consumption variables can be used to track long-term changes in behavioral, molecular or physiochemical mechanisms related to our understanding of diagnosis, prevention, intervention and treatment efficacies.

Genome-wide analysis of the nucleus accumbens identifies DNA methylation signals differentiating low/binge from heavy alcohol drinking

“…While macaques self-administer a broad range (0.5–4.4 g/kg/day) of alcohol during the 12 months of open access to ethanol and water, the present study focuses on the subjects among the lower end of this spectrum, those classified as “low” or “binge” drinkers (LDs and BDs, respectively) (Baker et al, 2014). Specifically, subjects were classified as BDs if they voluntarily consumed more than 2g/kg/day but less than 3 g/kg/day for more than 55% of the days during 12 months of access to 4% alcohol; subjects that did not reach the BD alcohol consumption threshold were defined as LDs (Supplementary Figure 1b).…”

“…Overall, all the L/BDs had a mean daily alcohol use of 1.9 g/kg (Supplementary Figure 1a). To determine whether the methylation changes observed in L/BDs were also present among subjects that consumed much more alcohol, we included additional subjects classified as “heavy” or “very heavy” drinkers based on their alcohol consumption levels in the same 12 month self-administration study (Baker et al, 2014). Here identified as heavy/very heavy drinkers (H/VHDs) these subjects consumed an average of between 2.4 and 4.4 g/kg/day.…”

“…Here identified as heavy/very heavy drinkers (H/VHDs) these subjects consumed an average of between 2.4 and 4.4 g/kg/day. Importantly, L/BDs never, or occasionally, reach BECs above 80 mg/dl, the baseline measure of human intoxication (Baker et al, 2014). In contrast, H/VHDs routinely measure BECs above 80 mg/dl.…”

“…The nonhuman primate (NHP) alcohol self-administration model provides unique opportunity to investigate the neural state associated with a broad range of alcohol consumption histories (from 0.5 g/kg/day to up to 4.4 g/kg/day; Baker et al, 2014). In this model, macaques are given open access to both 4% (w/v) ethanol and water ad libitum for 22 hours/day for 12 months, with precise daily recordings of all fluids and food consumed (Grant et al, 2008b).…”

“…Studies modeling the alcohol self-administration consumption patterns in macaques have identified four stable and distinguishable classifications, termed low, binge, heavy and very heavy drinking. Together, the low and binge drinkers consume an average of 1.9 g/kg/day alcohol and never (low) or only occasionally (binge) reach blood ethanol concentrations (BECs) above 80 mg/dl, the baseline measure of human intoxication (Baker et al, 2014). In contrast, the heavy and very heavy drinking subjects regularly consume 3.0 g/kg/day or greater and regularly reach BECs above 80 mg/dl.…”