Administration of a selective glucocorticoid antagonist attenuates electroconvulsive shock-induced retrograde amnesia

Abstract

Mifepristone, a glucocorticoid and progesterone receptor antagonist, has been shown to attenuate retrograde amnesia induced by repeated electroconvulsive shocks (ECS). We examined the efficacy of CORT 108297, a selective glucocorticoid antagonist, in this regard. Adult, male, Wistar rats (n=69) received either vehicle or CORT 108297 (1mg/kg) 2h before each of 5 once-daily true or sham 30mC ECS. Recall of previous exposure to a noxious stimulus in a passive avoidance (step-through) paradigm was tested 1day after the 5-ECS course. Analyses were conducted using recall operationalized in different ways: using the absolute final latency scores; defining adequate recall as a final latency of 30s or greater; defining perfect recall as a final latency of 180s; and using visual, subjective assessments of animal behavior. ECS was associated with significant impairment of recall, and this impairment was significantly attenuated by CORT 108297 on all outcome measures (with the exception of the perfect recall analyses, where outcomes narrowly missed statistical significance). In conclusion, these findings strengthen previous data from our laboratory implicating glucocorticoid mechanisms in ECS-induced retrograde amnesia. We suggest that the administration of a selective glucocorticoid receptor antagonist shortly before electroconvulsive therapy (ECT) treatments may attenuate the deleterious effect of ECT-induced acute hypercortisolemia on neural mechanisms involved in learning and memory.