Surgical and pharmacological suppression of glucocorticoids prevents the enhancement of morphine conditioned place preference by uncontrollable stress in rats

Rationale: Stress and one of the physiological components of most stress responses, glucocorticoid hormones (CORT), are known to influence the rewarding effects of a number of drugs of abuse. We have previously shown that an acute uncontrollable stressor (inescapable shock, IS) potentiates the rewarding effects of morphine using conditioned place preference (CPP). Objective: The following experiments were conducted to determine the role of CORT in this process. Methods: First, the CORT response to 3.0 mg/kg morphine was measured in male Sprague-Dawley rats 24 h following exposure to IS. Second, we determined the effect of adrenalectomy (ADX) on the IS-potentiated CPP to morphine. Finally, we used the temporary CORT synthesis inhibitors metyrapone and aminoglutethimide to determine the necessity of CORT rises during either IS or morphine administration on the potentiated CPP response. Results: Prior IS significantly potentiated the CORT response to morphine. ADX significantly blocked the potentiated CPP to morphine produced by previous IS. However, CORT inhibition during IS had no effect on the IS potentiation of morphine CPP, whereas inhibition during morphine administration completely blocked this potentiation. Conclusions: The results indicate that the CORT response to morphine is enhanced in rats that were previously exposed to an uncontrollable stressor, and that this response to the drug, not the stressor, is necessary for the stress-enhanced potentiation of morphine CPP.