EFFECT OF CHRONIC ADMINISTRATION OF PHENYTOIN ON REGIONAL MONOAMINE LEVELS IN RAT-BRAIN

Phenytoin (DPH) is a widely used anticonvulsant drug but a conclusive mode of action is not yet clear. This study was undertaken to assess t he effects of chronic administration of DPH on monoamine levels. DPH ( 50 mg/kg body weight) was administered to adult male Wistar rats by in traperitoneal injections for 45 days and the regional brain levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed u sing high performance liquid chromatographic (HPLC) method. The experi mental rats revealed no behavioral deficits of any kind nor body and b rain weight deficits were observed. Increased NE levels were observed after DPH administration in motor cortex (P<0.05), striatum-accumbens (P<0.01) and hippocampus (P<0.01), whereas, NE level was decreased in brain stem (P<0.05). DA levels were increased in striatum-accumbens (P <0.05), hypothalamus (P<0.001) and cerebellum (P<0.001) but decreased in brainstem (P<0.01). In DPH treated rats, 5-HT levels were increased in motor cortex (P<0.001) but decreased in cerebellum (P<0.001) when compared to control group of rats. The present study suggest that chro nic administration of DPH induces alterations in monoamine levels in s pecific brain regions. DPH seems to mediate its anticonvulsant action by selectively altering the monoamine levels in different brain region s.