Effect of chronic treatment of MPTP monkeys with dopamine D-1 and/or D-2 receptor agonists.
A severe parkinsonian syndrome developed in four monkeys after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). One monkeys subsequently remained untreated, and each of the three others were treated daily for at least one month with Sinemet, bromocriptine or SKF 38393. An intact control monkey (not MPTP-treated) was also included in the experiment. Sinemet and bromocriptine relieved the parkinsonian symptoms, whereas SKF 38393 was ineffective. The animal treated with Sinemet developed dyskinesia while those treated with bromocriptine or SKF 38393 did not. MPTP decreased dopamine levels by more than 99% in the striatum of all monkeys. Striatal D-1 and D-2 dopamine receptor densities as evaluated by autoradiography of [3H]SCH 23390 and [3H]spiperone binding were increased by 66 and 51%, respectively, after MPTP. Sinemet, bromocriptine or SKF 38393 treatment decreased D-2 receptor density, respectively, by 17, 84 and 35% and D-1 receptor density by 28, 33 and 6% vs. that in MPTP-treated animals. Our results suggest that dopamine receptor changes could be implicated in the loss of efficacy and in the side-effects of these treatments.
Gagnon
C
C
School of Pharmacy, Laval University, Quebec, Canada.
Bédard
P J
PJ
Di Paolo
T
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology; D001971:Bromocriptine / Q000494:pharmacology; D002230:Carbidopa / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D008252:Macaca fascicularis; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000494:pharmacology
D002395:Catecholamines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D001971:Bromocriptine; D007980:Levodopa; 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; D002230:Carbidopa