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

Full 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.

Author information

Author/s: Andrade, Chittaranjan (C); Singh, Nagendra M (NM); Thyagarajan, S (S); Nagaraja, Nandakumar (N); Sanjay Kumar Rao, N (N); Suresh Chandra, J (J);

Affiliation: Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India. andradec(-atsign-)gmail.com

Journal and publication information

Publication Type: Journal Article; Review

Journal: Journal of psychiatric research (J Psychiatr Res), published in England. (Language: eng)

Reference: 2008-Aug; vol 42 (issue 10) : pp 837-50

Dates: Created 2008/06/16; Completed 2008/08/25;

PMID: 17937934, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amnesia, Retrograde - physiopathology
Animals
Avoidance Learning - drug effects; physiology
Conditioning, Classical - drug effects; physiology
Cyclooxygenase 2 - physiology
Electroconvulsive Therapy - adverse effects
Glutamine - physiology
Hippocampus - drug effects; physiopathology
Indomethacin - pharmacology
Kynurenic Acid - metabolism

Lipid Peroxidation - drug effects; physiology
Long-Term Potentiation - drug effects; physiology
Male
Mental Recall - drug effects; physiology
Pyrazoles - pharmacology
Rats
Receptors, N-Methyl-D-Aspartate - drug effects; physiology
Signal Transduction - drug effects; physiology
Sulfonamides - pharmacology
Up-Regulation - drug effects; physiology

Associated Chemicals: Pyrazoles (0) ; Receptors, N-Methyl-D-Aspartate (0) ; Sulfonamides (0) ; celecoxib (169590-42-5) ; Kynurenic Acid (492-27-3) ; Indomethacin (53-86-1) ; Glutamine (56-85-9) ; Cyclooxygenase 2 (EC 1.14.99.1) ; Ptgs2 protein, rat (EC 1.14.99.1)

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