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-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 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. Copyright (C) 1999 Elsevier Science B.V.
|Number of pages||5|
|Journal||European Journal of Pharmacology|
|State||Published - Aug 13 1999|
Bibliographical noteFunding Information:
This work was supported by grants from the Parkinson Foundation of Canada (T.D.P. and P.J.B.) and the Medical Research Council of Canada (T.D.P. and P.J.B.). Richard Grondin and Martin Goulet held studentships from Le Fond de la Recherche en Santé du Québec (FRSQ).
- Dopamine D receptor
- Parkinson's disease
ASJC Scopus subject areas