The density of
dopamine D1 receptor antagonist sites was measured by autoradiography and
dopamine D1 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 D1 receptor agonist 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zep ine 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 D1 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 D1 receptor mRNA levels in the putamen appeared to decrease after
MPTP lesion and agonist treatment as compared to
dopamine D1 receptor density. In contrast, an apparent decrease in
dopamine D1 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 D1 receptors, respectively.