Regulation by chronic treatment with cabergoline of dopamine D1 and D2 receptor levels and their expression in the striatum of Parkinsonian-monkeys.
1. Chronic treatment for one month with the long-acting dopamine D2-like agonist cabergoline (0.25 mg/kg s.c. every 48 hours), had despite partial tolerance, sustained antiparkinsonian activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian monkeys (Macaca fascicularis). 2. Cabergoline treatment decreased by half striatal D2 receptor binding density measured by [3H]spiperone autoradiography versus untreated MPTP monkeys. No change in D2 mRNA measured by in situ hybridization and D2 receptor immunostaining was observed. 3. No change in either D1 receptor binding density or D1 receptor mRNA levels was observed in cabergoline-treated MPTP-monkeys compared to untreated MPTP-monkeys, suggesting receptor subfamily specificity of cabergoline. 4. The present results suggest that the cabergoline-induced behavioral partial tolerance is accompanied by a decrease in D2 receptor binding but not due to alterations in the steady state of D2 mRNA levels.
Goulet
M
M
Faculty of Pharmacy, Laval University and Department of Molecular Endocrinology, Laval University Medical Centre, Ste-Foy, Québec, Canada.
Grondin
R
R
Morissette
M
M
Maltais
S
S
Falardeau
P
P
Bédard
P J
PJ
Di Paolo
T
T
D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001665:Binding Sites; D000077465:Cabergoline; D004195:Disease Models, Animal; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D017403:In Situ Hybridization; D008252:Macaca fascicularis; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology
D000978:Antiparkinson Agents; D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000077465:Cabergoline