Alcohol response and consumption in adolescent rhesus macaques: life history and genetic influences

Abstract

The use of alcohol by adolescents is a growing problem and has become an important research topic in the etiology of the alcohol use disorders. A key component of this research has been the development of animal models of adolescent alcohol consumption and alcohol response. Because of their extended period of adolescence, rhesus macaques are especially well suited for modeling alcohol-related phenotypes that contribute to the adolescent propensity for alcohol consumption. In this review, we discuss studies from our laboratory that have investigated both the initial response to acute alcohol administration and the consumption of alcohol in voluntary self-administration paradigms in adolescent rhesus macaques. These studies confirm that adolescence is a time of dynamic change both behaviorally and physiologically, and that alcohol response and alcohol consumption are influenced by life history variables, such as age, sex, and adverse early experience in the form of peer-rearing. Furthermore, genetic variants that alter functioning of the serotonin, endogenous opioid, and corticotropin-releasing hormone systems are shown to influence both physiological and behavioral outcomes, in some cases interacting with early experience to indicate gene by environment interactions. These findings highlight several of the pathways involved in alcohol response and consumption, namely reward, behavioral dyscontrol, and vulnerability to stress, and demonstrate a role for these pathways during the early stages of alcohol exposure in adolescence.

Figure 1

Lack of an effect of early exposure to alcohol on later alcohol consumption. Subjects (n = 53) were tested in the social group condition for 1 hour a day, five days a week, for 4 weeks when they were 4-5 years of age. A subset of subjects (n = 30) had been similarly tested in the single cage condition when they were about 2.5 years of age. Analysis was performed using repeated measures ANOVA, with testing week as the within subjects variable and sex and early exposure (yes/no) as the between subjects variables. Precise age at the time of testing in the social group was also included as a covariate. Data are presented as mean (± SEM) alcohol consumption for each testing week. There was no main effect of sex F(1,48) = 3.91; P = 0.06 and no main effect of early exposure F(1,48) = 0.72; P = 0.40, nor any interactive effects of early exposure with sex F(1,48) = 0.04; P = 0.84 or with week of testing F(3, 144) = 0.11; P = 0.95.

Figure 2

Rearing condition influences alcohol intake in the single cage but not the social group setting. Data on 211 monkeys from the limited-access, voluntary self-administration paradigm were analyzed using 2-way ANOVA, with rearing history, sex, and testing condition as independent variables and mean alcohol consumption (g/kg) across testing weeks as the dependent variable. Data are presented as means ± SEM. There was a main effect of rearing history F(1,202) = 23.47; P = 0.00003, a main effect of testing condition F(1,202) = 158.85; P = 0.00000, and an interaction between rearing history and testing condition F(1,202) = 14.66; P = 0.0002. Post-hoc tests revealed significant differences between peer-reared and mother-reared subjects in the single cage condition, as well as differences between the single cage and social setting conditions within each rearing group (Neuman-Keuls tests, all p < 0.05).