Possible glutamatergic and lipid signalling mechanisms in ECT-induced retrograde amnesia: Experimental evidence for involvement of COX-2, and review of literature

Chittaranjan Andrade, Nagendra M. Singh, S. Thyagarajan, Nandakumar Nagaraja, N. Sanjay Kumar Rao, J. Suresh Chandra

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32 Scopus citations

Abstract

We sought to explore nonselective vs. selective COX mechanisms in ECS-induced retrograde amnesia using indomethacin and celecoxib as in vivo probes. Adult Wistar rats (n = 72) which showed adequate learning on a passive avoidance task received 5 once-daily 30 mC true or sham ECS. During the learning and ECS periods, indomethacin (4 mg/kg/day), celecoxib (15 mg/kg/day), or vehicle were orally administered. One day after the fifth ECS, recall of pre-ECS learning was tested. There were no baseline or pre-ECS differences in learning between groups. ECS seizure duration did not differ across groups. ECS-treated rats showed impaired recall in the vehicle but not indomethacin and celecoxib groups. Celecoxib but not indomethacin significantly protected against ECS-induced retrograde amnesia. We interpret these results as follows: ECS may impair cognition by pathologically upregulating glutmatergic signalling, thereby causing cation and water influx, oxidative stress, and saturation of hippocampal LTP. These may result from glutamatergic disinhibition through COX-2-mediated removal of endogenous cannabinoids, and by ECS-activated, NMDA-mediated upregulation of platelet activating factor and COX-2 signalling pathways. Thus, indomethacin and celecoxib, by inhibiting COX-2, may protect against ECS-induced amnesia. Furthermore, COX-2 mediated increase in hippocampal kynurenic acid may impair glutamate-dependent learning and memory processes at ionotropic glutamatergic receptor sites; the inhibition of kynurenic acid synthesis by celecoxib and its induction by indomethacin may explain the greater benefits with celecoxib. These findings suggest new avenues for the study of the neurobiology of ECT-induced amnesia and the attenuation thereof.

Original languageEnglish (US)
Pages (from-to)837-850
Number of pages14
JournalJournal of Psychiatric Research
Volume42
Issue number10
DOIs
StatePublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

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