Rationale: Glucocorticoids have been reported to have rewarding effects in rats and may lead to drug-seeking behavior in humans under some circumstances. Objectives: The present study investigated whether glucocorticoids would be self-administered intravenously by rhesus monkeys (Macaca mulatta). Methods: Ten monkeys, 7 male and 3 female, were maintained on a fixed ratio 10 (30 or 100), time-out 10-s schedule for 0.1 mg/kg methohexital or saline injections. Dexamethasone (0.03–0.3 mg/kg), methylprednisolone (0.1–1.0 mg/kg) and hydrocortisone (0.3–3.0 mg/kg) were periodically substituted for methohexital or saline. Results: Dexamethasone (0.3 mg/kg) was self-administered by all of the male monkeys on the first, but not on subsequent occasions. It was hypothesized that suppression of hypothalamic–pituitary–adrenal (HPA) activity by these exogenous glucocorticoids following their first presentation may have interfered with their reinforcing effects on subsequent evaluation. Subsequently, plasma adrenocorticotropin and cortisol were measured in four male monkeys to ascertain that normal basal HPA activity had resumed prior to each glucocorticoid substitution. Of the ten monkeys that were tested, only one reliably self-administered dexamethasone, methylprednisolone and hydrocortisone, and he did so regardless of whether his basal HPA activity was suppressed. This monkey differed from some of the other monkeys both behaviorally and in his response to intravenous corticotropin releasing hormone. None of the three female monkeys that were tested with selected glucocorticoid doses showed any evidence of glucocorticoid reinforcement on any occasion. Conclusions: The results indicate that glucocorticoids were not reinforcing to the majority of monkeys in this study; nevertheless, large individual differences may exist in proclivity of monkeys to self-inject these compounds
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