Chronic treatment with MK-801 increases the quinolinic acid-induced loss of D-1 dopamine receptors in rat striatum

Abstract

Following withdrawal from short-term treatment with the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 (1 mg/kg per day) there was no significant change in the B max or K D of [ 3H]SCH23390 binding to dopamine D-1 receptors in rat striatum. Intrastriatal injection of the excitotoxin quinolinic acid (100 nmol) produced a significant decrease in [ 3H]SCH23390 binding. In rats withdrawn from chronic MK-801 treatment quinolinic acid produced a significantly greater loss of [ 3H]SCH23390 binding sites than in rats not treated with MK-801. These data indicated that striatal neurons are hypersensitive to the neurotoxic actions of quinolinic acid following withdrawal from chronic MK-801 treatment.