Celecoxib as an in vivo probe of cyclooxygenase-2 mechanisms underlying retrograde amnesia in an animal model of ECT
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Cyclooxygenase-2 (COX-2) mechanisms are involved in glutamate-mediated learning and memory as well as in glutamatergic excitotoxicity. Electroconvulsive therapy (ECT)-induced amnesia may arise from glutamatergic excitotoxicity; if so, COX-2 inhibition may attenuate retrograde amnesia with ECT.
Wistar rats which received celecoxib (15 mg/kg per day) or vehicle for 18 days were trained for 3 days on a passive avoidance task. On each of the next 3 days, rats which showed perfect learning (n = 51) received true or sham suprathreshold electroconvulsive shocks (ECS; 60 mC) in a factorial design; daily dosing with drug or vehicle was continued. One day after the last ECS, recall of pre-ECS learning was tested.
ECS-treated rats showed impaired recall in the vehicle but not celecoxib group. Celecoxib significantly protected against ECS-induced retrograde amnesia; this benefit was independent of the drug-induced attenuation of ECS seizure duration.
Celecoxib may protect against ECS-induced retrograde amnesia by attenuating ECS-induced, COX-2-mediated glutamatergic excitotoxicity.
KeywordsElectroconvulsive therapy Learning Memory Celecoxib COX-2 Glutamate
Author S. Thyagarajan was supported by an unrestricted grant from the non-profit Scion Natural Science Association, St James, New York, USA.
Conflict of interest statement
There are no financial or other conflicts of interest except as stated in the acknowledgement.
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