Dopamine D1 receptor mRNA and receptor levels in the striatum of MPTP monkeys chronically treated with SKF-82958.
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.
Grondin
R
R
Faculty of Medicine, Laval University, Quebec City, Canada.
Goulet
M
M
Morissette
M
M
Bédard
P J
PJ
Di Paolo
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D008252:Macaca fascicularis; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D001552:Benzazepines; D015259:Dopamine Agents; D018491:Dopamine Agonists; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; C071262:SK&F 82958; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine