Celecoxib as an in vivo probe of cyclooxygenase-2 mechanisms underlying retrograde amnesia in an animal model of ECT.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Celecoxib may protect against ECS-induced retrograde amnesia by attenuating ECS-induced, COX-2-mediated glutamatergic excitotoxicity.
Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India. andrade@nimhans.kar.nic.in
Chittaranjan
C
Andrade
Shivashanmugam
S
Thyagarajan
Nagendra Madan
NM
Singh
Pabbisetty S
PS
Vinod
N
N
Sanjay Kumar Rao
J Suresh
JS
Chandra
D000648:Amnesia, Retrograde / Q000209:etiology* / Q000517:prevention & control*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D004597:Electroshock / Q000009:adverse effects*; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D011720:Pyrazoles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000627:therapeutic use*
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib