Glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia.
BACKGROUND
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.


OBJECTIVE
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.


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.


CONCLUSIONS
Mifepristone administered before the ECT seizure may attenuate ECT-induced retrograde amnesia. This suggests that glucocorticoid mechanisms may contribute to ECT-induced retrograde amnesia.
Nagaraja
Nandakumar
N
Department of Pharmacology, St John's Medical College, Bangalore, India.
Andrade
Chittaranjan
C
Sudha
Suresh
S
Madan Singh
Nagendra
N
Chandra
J Suresh
JS
Venkataraman
B V
BV
D000648:Amnesia, Retrograde / Q000503:physiopathology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006727:Hormone Antagonists / Q000494:pharmacology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000502:physiology*
D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone