ANTICONVULSANT ACTION OF SCH-23390 IN THE STRIATUM OF THE RAT

This study investigates the role of forebrain D1 receptors in the motor expression of seizures induced by pilocarpine. Conscious rats receiving bilateral intracaudate injections of saline, just failed to convulse to 200 mg/kg pilocarpine, but responded vigorously to 600 mg/kg of the cholinomimetic. LT 171555 significantly protected rats against 600 mg/kg pilocarpine, when delivered into the anterior striatum, as also did SCH 23390, from all rostrocaudal levels of the striatum. Intrastriatal SKF 38393 or CY 208-243 neither facilitated nor ameliorated pilocarpine-induced convulsions. SCH 23390 was also anticonvulsant from the nucleus accumbens, while intra-accumbens CY 208-243 was without effect. It is concluded that SCH 23390 affords protection against pilocarpine-induced limbic motor seizures by blocking the effects of endogenous dopamine released tonically onto D1 receptors in the corpus striatum and nucleus accumbens. The inability of additional D1 receptor stimulation to intensify such seizures, could indicate that forebrain D1 receptors are already maximally stimulated by the endogenous transmitter.