Effect of carbamazepine on cholinergic parameters in rat brain areas

Abstract

The action of the anti-epileptic drug, carbamazepine, was studied on the cholinergic tetrad (acetylcholine, choline, choline o-acetyltransferase and cholinesterase) in rat brain areas. The drug increased striatal acetylcholine starting at an intraperitoneal dose of 15 mg/kg. The maximal increase in striatal acetylcholine of 66% was produced at 25 mg/kg and the effect persisted for at least 120 min. This action was selective for the striatum, there being no effect in other brain regions encompassing the mesencephalon, diencephalon, cerebellum and hippocampus. The hemispheric residuum (after removal of the striatum and hippocampus) showed a 45% increase in acetylcholine but only at the highest dose used, 50 mg/kg. The choline level was decreased markedly in both the striatum and hemispheric residuum by carbamazepine at a dose of 25 mg/kg. Neither carbamazepine nor its metabolite, carbamazepine-10,11-epoxide affected striatal choline o-acetyltransferase or cholinesterase after in vitro incubation. The increase in striatal acetylcholine by carbamazepine was not mediated through the dopaminergic system, since pretreatment with pimozide, a powerful dopaminergic antagonist, did not prevent the effect. No tolerance to the action of carbamazepine on striatal acetylcholine was produced after chronic treatment with 25 mg/kg twice per day for 6 days.