Stress is believed to be an etiological factor in the abuse of ethanol. Chronic and acute stress are known to alter the behavioral effects of ethanol, including the reinforcing effects. Available evidence also suggests that chronic stress alters neurotransmission in specific brain regions that are important for mediating the reinforcing effects of many drugs of abuse, including ethanol. However, there is a need to more completely characterize the limbic, hypothalamic, pituitary and adrenal response to stress an how this response predicts heavy ethanol self-administration. In addition, the source of stress can determine the endocrine and nervous systems response and adaptation. Macaque monkeys are social animals and form stable, liner, social dominance hierarchies. The relative rank of an individual within social hierarchies has trait-like qualities and remains constant, even if the monkeys are separated for some time. Many studies have shown that social subordination in macaque troops results in elevated signs of stress. Socially-derived stress in monkeys can be categorized as psychogenic and, in subordinate monkeys, uncontrollable. Stress of this nature is most associated with stress-induced psychiatric pathology, including alcoholism. We propose to investigate the effects of socially-derived stress, specifically social subordination and limited social contact on ethanol self-administration. We have developed a model of alcohol self-administration in macaque monkeys that produces excessive ethanol? consumption in a proportion of the population. The heavy drinkers are largely male and consume an average of 3.0-4. 0 g/kg/day (I 2-16 drinks/day) with average blood ethanol concentrations of 160 mg% 8 hours into the daily drinking episode. With this model we propose to characterize the limbic, hypothalamic, pituitary and adrenal response to stress in naive monkeys and then explore how this response predicts heavy ethanol self-administration.
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