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Effect of Stimulus Intensity and Number of Treatments on ECS-Related Seizure Duration and Retrograde Amnesia in Rats

Andrade, Chittaranjan M.D.*; Thyagarajan, S. B.Pharm; Vinod, P. S. B.Pharm; Srikanth, S. N. B.Pharm (in progress); Rao, N. S. K. M.D.§; Chandra, J. Suresh M.V.Sc.

Original Articles

Background Animal models are frequently used to generate and test hypotheses about amnesia resulting from electroconvulsive therapy (ECT). Although many predictors of ECT-induced amnesia are known, their relative effects have been inadequately researched in the context of the animal models.

Objective We sought to determine the relative retrograde amnestic effects of electroconvulsive shock (ECS) stimulus intensity (dose) and number on strong memories in rats. We also sought to identify dose-dependent ceiling amnestic effects, if any.

Methods Adult rats (n = 144) were overtrained in a passive avoidance task using a step down apparatus. The rats were then randomized in a factorial design to receive one, two, or three once-daily bilateral ECS at 0-mC (sham ECS), 30-mC, 60-mC, 120-mC, or 180-mC doses. Recall of the pre-ECS training was assessed 1 day after the last ECS.

Results Retrograde amnesia was observed only in rats that received 3 ECS; dose-dependent amnestic effects did not emerge. Higher stimulus intensity was associated with a small (13%) but significant increase in motor seizure duration, but only at the first ECS; stimulus intensity did not influence the attenuation of seizure duration across repeated occasions of ECS.

Conclusion With bilateral ECS, the number of ECSs administered is a more important variable than the ECS dose in weakening a strong, recently acquired, noxious memory; this finding may have important clinical implications. Higher stimulus intensity marginally increases motor seizure duration at the first ECS but does not influence the decrease in seizure duration across repeated ECSs.

*Department of Psychopharmacology and Central Animal Research Facility, National Institute of Mental Health and Neurosciences; †Oxford Institute of Pharmacy; and ‡Visveswarapura Institute of Pharmaceutical Sciences, Bangalore, India; and §Liaison Psychiatry Mental Heath Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, United Kingdom

Received April 30, 2002; accepted September 16, 2002.

Address correspondence and reprint requests to Chittaranjan Andrade, M.D., Department of Psychopharmacology, NIMHANS, Bangalore 560 029, India. E-mail: or

© 2002 Lippincott Williams & Wilkins, Inc.