Rationale: Cortisol levels rise sharply immediately after electroconvulsive therapy (ECT); the resultant stimulation of steroid receptors in the hippocampus may be beneficial or harmful to cognition, depending on the magnitude of the stimulation. Steroid mechanisms may therefore modulate ECT-induced amnesia. Objectives: Using mifepristone (a glucocorticoid receptor antagonist) as a chemical probe, we sought to examine steroid mechanisms in an animal model of ECT-induced retrograde amnesia. Materials and methods: Adult, male Wistar rats (n = 68) trained in a step-through passive-avoidance task were randomized to receive mifepristone (20 or 40 mg kg-1 day -1) or vehicle (control). These treatments were administered 1 day before the electroconvulsive shock (ECS) course and, again, 1 h before each of five once-daily true (30 mC) or sham ECS. Recall of pre-ECS learning was tested 1 day after the last ECS. Results: Relative to sham ECS, true ECS resulted in significant retrograde amnesia in the vehicle group but not in either of the mifepristone groups. In sham ECS-treated animals, mifepristone did not significantly influence recall. In ECS-treated rats, the higher but not the lower dose of mifepristone was associated with significant protection against the retrograde amnesia evident in the vehicle group. Conclusion: Mifepristone administered before the ECT seizure may attenuate ECT-induced retrograde amnesia. This suggests that glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia.
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