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 (1 mg/kg) 2 h before each of 5 once-daily true or sham 30 mC ECS. Recall of previous exposure to a noxious stimulus in a passive avoidance (step-through) paradigm was tested 1 day 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 30 s or greater; defining perfect recall as a final latency of 180 s; 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.

• Authors: Chittaranjan Andrade, Shahid Ahmad Shaikh, Lakshmy Narayan, Christine Blasey, Joseph Belanoff
• Journal: Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 119 Issue 3 Pg. 337-44 (Mar 2012) ISSN: 1435-1463 [Electronic] Austria
• PMID: 21922193 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aza Compounds
• CORT 108297
• Heterocyclic Compounds, 4 or More Rings
• Receptors, Glucocorticoid

Topics

• Amnesia, Retrograde (drug therapy, etiology)
• Animals
• Aza Compounds (pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Electroshock (adverse effects)
• Heterocyclic Compounds, 4 or More Rings (pharmacology, therapeutic use)
• Male
• Memory (drug effects)
• Rats
• Rats, Wistar
• Receptors, Glucocorticoid (antagonists & inhibitors)