Behavioral and biochemical effect of chronic treatment with D-1 and/or D-2 dopamine agonists in MPTP monkeys.
Monkeys developed a severe parkinsonian syndrome after intravenous administration of (MPTP). L-DOPA/carbidopa (D-1 and D-2) or bromocriptine (D-2) treatment relieved the parkinsonian symptoms, whereas SKF 38393 (D-1) was ineffective. No dyskinesia was seen in monkeys receiving bromocriptine or SKF 38393 as opposed to the L-DOPA-treated animals, in which the dyskinetic response appeared to increased with time. MPTP induced a significant increase (25%, P less than 0.01) in the number of [3H]spiperone binding sites (Bmax) in the caudate nucleus and in putamen. The Bmax of spiperone binding in the L-DOPA-treated monkeys was on average 18% lower (P less than 0.01) than that of the animals treated with MPTP alone. The Bmax for the bromocriptine-treated group was 29% (P less than 0.01) less than that in the MPTP-treated group or 11% (P less than 0.05) less than that in the L-DOPA-treated monkeys. The SKF 38393 treatment induced a 23% (P less than 0.01) decrease in the Bmax as compared to that of animals treated with MPTP alone, and no significant change compared to the L-DOPA- or bromocriptine-treated animals. These results suggest that stimulation of D-1 and D-2 dopamine receptors can differently influence the mechanisms controlling dopamine agonist-induced dyskinesia in MPTP-treated monkeys.
Falardeau
P
P
School of Pharmacy, Laval University, Québec, Canada.
Bouchard
S
S
Bédard
P J
PJ
Boucher
R
R
Di Paolo
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D008252:Macaca fascicularis; D009043:Motor Activity / Q000187:drug effects*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011725:Pyridines / Q000633:toxicity*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism
D001552:Benzazepines; D011725:Pyridines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D013134:Spiperone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid