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Glucocorticoids, adrenal medullary opioids, and the retention of a behavioral response after stress.

In the Porsolt model swimming test, naive rats become progressively more immobile over a 15-min initial test (0-5 min, approximately 30% immobile; 5-10 min, approximately 50%, 10-15 min, approximately 70%). Twenty-four hours later, rats have retained the response, being immobile for about 70% of a 5-min retest period. We previously reported that in this test adrenalectomized rats are indistinguishable from intact rats over the 15-min test period, but are immobile for only approximately 30% of a 5-min retest period 24 h later. The finding that this behavioral effect of adrenalectomy can be reversed by glucocorticoids or kappa-selective opioids led us to hypothesize that retention of the immobile behavior can be effected by glucocorticoids from the adrenal cortex or kappa-selective opioids from the adrenal medulla. To test this hypothesis, we have given intact rats the antiglucocorticoid RU38486 and the anticholinergics atropine and mecamylamine to block adrenal medullary discharge, either alone or simultaneously. Administered alone, neither class of antagonist affected the response; administered together, they profoundly reduced immobility to levels seen in adrenalectomized rats. Additional evidence for medullary kappa-selective opioids mediating the behavioral effect was that the administration to hypophysectomized rats of atropine plus mecamylamine or the kappa-selective antagonist MR2266 reduced immobility to the levels seen in adrenalectomized animals. We conclude that secretion from either the adrenal cortex or medulla is sufficient for the incorporation of this learned response after stress, and that in intact animals input from both zones may contribute to the terms of this behavioral response.