Dopamine D 1 receptor mRNA and receptor levels in the striatum of MPTP monkeys chronically treated with SKF-82958

Abstract

The density of dopamine D 1 receptor antagonist sites was measured by autoradiography and dopamine D 1 receptor mRNA levels were measured by in situ hybridization in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed monkeys chronically treated with the dopamine D 1 receptor agonist 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrobromide (SKF-82958) administered in intermittent or continuous mode for a month. Normal and MPTP-exposed but otherwise untreated animals were used for comparison. Intermittent treatment with SKF-82958 relieved parkinsonian features and induced dyskinesias whereas given continuously this drug induced behavioral tolerance without dyskinesias. On the one hand, MPTP treatment tended to increase dopamine D 1 receptor density in the putamen whereas treatment of MPTP monkeys with SKF-82958, intermittent or continuous, produced a significant increase compared to control animals. On the other hand, dopamine D 1 receptor mRNA levels in the putamen appeared to decrease after MPTP lesion and agonist treatment as compared to dopamine D 1 receptor density. In contrast, an apparent decrease in dopamine D 1 receptor density and mRNA levels was observed in the nucleus accumbens of untreated MPTP monkeys whereas treatment of MPTP monkeys with SKF-82958, intermittent or continuous, produced a significant decrease compared to control animals. Thus, neither dyskinesias nor tolerance can be exclusively related to an increase or decrease in striatal dopamine D 1 receptors, respectively.