ADRENOCORTICAL SUPPRESSION BLOCKS THE MEMORY-ENHANCING EFFECTS OF AMPHETAMINE AND EPINEPHRINE

This study examined glucocorticoid-adrenergic interactions in modulati ng acquisition and memory storage for inhibitory avoidance training. S ystemically (s.c.) administered amphetamine (1 mg/kg), but not epineph rine (0.1 mg/kg) or the peripherally acting amphetamine derivative 4-O H amphetamine (2 mg/kg), given to rats shortly before training facilit ated acquisition performance in a continuous multiple-trial inhibitory avoidance (CMIA) task. Adrenocortical suppression with the 11 beta-hy droxylase inhibitor metyrapone (50 mg/kg; s.c), given to rats 90 min b efore training, did not block the effect of amphetamine and did not af fect acquisition performance of otherwise untreated animals. Retention of CMIA and one-trial inhibitory avoidance was enhanced by either pre - or posttraining injections of amphetamine, as well as 4-OH amphetami ne and epinephrine. The finding that injections of amphetamine and epi nephrine have comparable effects on memory is consistent with the view that amphetamine may modulate memory storage, at least in part, by in ducing the release of epinephrine from the adrenal medulla. Metyrapone pretreatment blocked the memory-enhancing effects of amphetamine, 4-O H amphetamine, and epinephrine but did not affect retention performanc e of otherwise untreated animals. Posttraining injections of different doses of epinephrine (ranging from 0.0001 to 1.0 mg/kg) produced a do se-dependent memory enhancement for inhibitory avoidance training and metyrapone blocked the memory-enhancing effects of all these doses. Th ese findings provide further evidence that the sympathoadrenal and adr enocortical systems are intimately coupled during processes of memory storage.