Central nervous system monoamine metabolite response to alcohol exposure is associated with future alcohol intake in a nonhuman primate model (Macaca mulatta)
ADDICTION BIOLOGY(2022)
摘要
It is widely held that the central monoamine neurotransmitters modulate alcohol intake. Few studies, however, directly assess the relationship between baseline and alcohol-induced monoamine turnover, as well as the change from baseline, as predictors of alcohol intake. Using a nonhuman primate model, this study investigates baseline, alcohol-induced and alcohol-induced change in monoamine activity and their relationship with alcohol intake. Alcohol-naive, adolescent rhesus macaques (Macaca mulatta, N = 114) were administered a standardized intravenous bolus of alcohol solution (16.8%, v/v) on two occasions, approximately 1 month apart. One month prior to and 1 h following each alcohol infusion, cisternal cerebrospinal fluid (CSF) was obtained and assayed for monoamine metabolite concentrations. Approximately 6-7 months later, subjects were allowed unfettered access to an aspartame-sweetened alcohol solution (8.4%, v/v) for 1 h/day, 5 days/week, over 5-7 weeks. Results showed strong positive correlations between baseline and post-infusion CSF monoamine metabolite concentrations, indicating a trait-like response. Low baseline and post-infusion serotonin and dopamine metabolite concentrations and a smaller change in serotonin and dopamine metabolites from one infusion to the next were associated with higher alcohol intake. Low baseline and post-infusion norepinephrine metabolite concentrations predicted high alcohol intake, but unlike the other monoamines, a greater change in norepinephrine metabolite concentrations from one infusion to the next was associated with higher alcohol intake. These findings suggest that individual differences in naturally occurring and alcohol-induced monoamine activity, as well as the change between exposures, are important modulators of initial alcohol consumption and may play a role in the risk for excessive alcohol intake.
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关键词
alcohol, dopamine, monoamines, norepinephrine, rhesus monkeys, serotonin
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