The role of glucocorticoids in the uncontrollable stress-induced potentiation of nucleus accumbens shell dopamine and conditioned place preference responses to morphine

SummaryExposure to stressors can impact on the responsiveness to drugs of abuse, and glucocorticoid hormones (CORT) may interact with dopamine (DA) within the nucleus accumbens shell (NAcs) to mediate these responses. We have previously shown that the CORT response to morphine, but not to a previous uncontrollable stressor, is necessary for the stress-induced potentiation of morphine's rewarding effects. Here, we test (1) the necessity of CORT during inescapable stress (IS) and/or morphine for IS potentiation of morphine-induced NAcs DA and (2) the sufficiency of enhanced CORT, in the absence of prior IS, to potentiate morphine-induced NAcs DA as well as morphine conditioned place preference (CPP) in male Sprague–Dawley rats. In the first experiment, we administered the CORT synthesis inhibitors metyrapone and aminoglutethimide (100 mg/kg each, sc) to suppress the CORT response to either IS (100 1 mA tailshocks) or subsequent morphine (3 mg/kg, sc) treatment. Twenty-four hour after IS, microdialysis was performed and morphine was administered. In the next experiments, CORT (1 mg/kg, sc) was injected 20 or 30 min before morphine during either microdialysis or CPP testing, respectively, in non-stressed rats. We found that IS potentiated subsequent morphine-induced NAcs DA and this was completely blocked by CORT suppression before morphine, but not before IS. However, elevated levels of CORT concurrent with morphine, but in the absence of a stressor, failed to potentiate NAcs DA or CPP. These results suggest that the CORT response to morphine is necessary, but not sufficient in the absence of prior IS, for sensitized NAcs DA and CPP responding to morphine, and provide further evidence that CORT is involved in the expression, but not the induction, of this sensitization.