Effect of stress on opioid-seeking behavior: evidence from studies with rats.

Studies concerned with the relation between exposure to stress and the behavioral effects of opioid agonists in animal models of drug use are reviewed. These studies, which primarily utilized male rats, indicate that under certain conditions short-term mild stressors increase self-administration of opioid drugs and reinstate herein-seeking behavior following a drug-free period. On the other hand, there is evidence that long-term chronic inescapable stressors and severe acute stressors reduce the reinforcing effects of morphine as measured by a conditioned place preference procedure and decrease the behavioral effects of other positive reinforcers. The results of the studies reviewed suggest that stressors are important modulators of opioid-taking behavior, especially during drug-free periods. The implications of these findings to the understanding of the neurobiology of relapse to opioid-seeking behavior and for strategies for medication development to prevent relapse to heroin are discussed.