Anticonvulsant activity of the cyclooxygenase-2 (COX-2) inhibitor etoricoxib in pentylenetetrazole-kindled rats is associated with memory impairment

Abstract

PurposeVarious selective and nonselective cyclooxygenase (COX) inhibitors are known to have effects on development and progression of seizures. In the present study, the effect of the selective COX-2 inhibitor etoricoxib on seizures, oxidative stress, and learning and memory was studied. MethodMale Wistar rats were kindled using subconvulsant dose of pentylenetetrazole (PTZ) (30mg/kg, i.p.), on alternating days until animals were fully kindled. After a one-week PTZ-free period, kindled rats were challenged with PTZ 30mg/kg, and the latency, duration, and severity of seizures were recorded. Etoricoxib was then administered intraperitoneally at 1mg/kg and 10mg/kg in kindled rats for nine days (days 6–14). On the ninth day of etoricoxib treatment, PTZ challenge (30mg/kg) was given, and seizure parameters were noted. On day 15, behavioral assessment was carried out. The Morris water maze (MWM) apparatus and the passive avoidance (PA) apparatus were used for studying cognitive impairment. The rats were then sacrificed, and malondialdehyde (MDA) and glutathione (GSH), markers of oxidative stress, were estimated in the brain samples. ResultsEtoricoxib at lower dose (1mg/kg) had an anticonvulsant effect which was reduced or reversed at higher dose (10mg/kg). Etoricoxib also impaired the learning and memory in rats as tested by passive avoidance and Morris water maze tests. ConclusionThe results of the present study suggest that use of etoricoxib, especially at low dose, in patients with epilepsy may not be detrimental with regard to seizure control. However, attention should be paid to cognitive parameters.