INIA: Stress and Ethanol Self-Administration in Monkeys

DESCRIPTION (provided by applicant):
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.