Glucocorticoid-reinforced responding in the rhesus monkey

Rationale: Glucocorticoids have been reported to have rewarding effects in rats and may lead to drug-seeking behavior in humans under some circumstanc es. Objectives: The present study investigated whether glucocorticoids woul d be self-administered intravenously by rhesus monkeys (Macaca mulatta). Me thods: Ten monkeys, 7 male and 3 female, were maintained on a fixed ratio 1 0 (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 me thohexital or saline. Results: Dexamethasone (0.3 mg/kg) was self-administe red by all of the male monkeys on the first, but not on subsequent occasion s. It was hypothesized that suppression of hypothalamic-pituitary-adrenal ( HPA) activity by these exogenous glucocorticoids following their first pres entation may have interfered with their reinforcing effects on subsequent e valuation. Subsequently, plasma adrenocorticotropin and cortisol were measu red in four male monkeys to ascertain that normal basal HPA activity had re sumed prior to each glucocorticoid substitution. Of the ten monkeys that we re tested, only one reliably self-administered dexamethasone, methylprednis olone and hydrocortisone, and he did so regardless of whether his basal HPA activity was suppressed. This monkey differed from some of the other monke ys both behaviorally and in his response to intravenous corticotropin relea sing hormone. None of the three female monkeys that were tested with select ed glucocorticoid doses showed any evidence of glucocorticoid reinforcement on any occasion. Conclusions: The results indicate that glucocorticoids we re not reinforcing to the majority of monkeys in this study; nevertheless, large individual differences may exist in proclivity of monkeys to self-inj ect these compounds.