Chronic antipsychotic treatment alters glycine-stimulated NMDA receptor binding in rat brain.

In this study the chronic effect of antipsychotic drugs (APDs) on N-methyl-D-aspartate (NMDA) receptor binding was evaluated. Rats were treated for 21 days with i.p. injections of haloperidol (0.5 mg/ kg), pimozide (0.5 mg/kg), clozapine (20 mg/kg), risperidone (1 mg/kg) or water vehicle (1 ml/kg). Brain tissue sections underwent different [3H]MK-801 assay conditions. Following a short preincubation wash, there were no effects of APDs on either unenhanced or agonist enhanced [3H]MK-801 binding. Following a prolonged preincubation wash, APDs resulted in a reduction in both unenhanced binding and glycine enhanced binding. The attenuation of glycine stimulation in the APD treated animals was selective as neither NMDA nor spermidine enhanced binding was significantly affected. The present data suggest specific actions at the glycine regulatory site on the NMDA receptor as part of the chronic effects of APDs.