The goal of this proposal is to achieve a better understanding of the individual differences in the susceptibility and vulnerability to the reinforcing effects of cocaine in a nonhuman primate model of drug abuse. Previous research with group-housed macaques has shown that susceptibility to disease states, such as atherosclerosis and viral infection, is influenced by social variables, such as reorganization of social groups and social status (i.e., dominant vs. subordinate). In addition, social stress has been shown to modify dopaminergic function. Results from other studies have shown that dopamine (DA) neurotransmission mediates, in large part, the reinforcing effects of cocaine and that reactivity to stress can increase midbrain DA activity and augment acquisition of drug reinforcement in rodents. However, there is no information regarding individual susceptibility to cocaine reinforcement in socially-housed nonhuman primates. The studies proposed in this application are designed to examine, in male cynomolgus monkeys (M. fascicularis), how social status and social stress caused by group reorganization influence the reinforcing effects of cocaine. These experiments will provide valuable within-subject data on several behavioral and physiological variables that may influence cocaine's reinforcing effects. Specifically, we propose to determine whether: 1) behavioral or physiological indices of stress predict social status in male cynomolgus monkeys; we hypothesize that highly reactive monkeys in the open field apparatus will show greater basal levels of cortisol and, when placed in social groups, will be subordinate to the other animals; 2) individual differences in social status predict individual differences in acquisition, maintenance, and relapse to cocaine reinforcement; we hypothesize that the reinforcing effects of cocaine will be greater in dominant monkeys as compared to subordinate animals; 3) individual differences in social status and cocaine self-administration are modified by elevated levels of stress induced by social reorganization; we hypothesize that social reorganization will have greater effects on cocaine self-administration in dominant compared to subordinate animals; 4) individual differences in social status and responses to social reorganization predict differences in the dopaminergic system; we will use the noninvasive imaging procedure of Positron Emission Tomography (PET), to study changes in dopamine D2 receptors, in all monkeys through all phases of the experiments. A better understanding of the variables that contribute to enhanced sensitivity to the reinforcing effects of cocaine may lead to better behavioral and/or pharmacological strategies for the treatment and prevention of cocaine abuse.
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