MPTP-Induced hemiparkinsonism in nonhuman primates 6-8 years after a single unilateral intracarotid dose.
Five female adult Macaca nemestrina monkeys, given a unilateral intracarotid (ic) infusion of 2.3-3.5 mg of MPTP-HCl, were studied for 6-8 years. Two to 3 days after MPTP, the animals developed hemiparkinsonism characterized by rigidity and flexed posture of the arm contralateral to the side of infusion with episodes of tremor, circling ipsilateral to the lesioned side, a slight balance disturbance, and stooped posture. Rating of parkinsonian features 4 months after ic infusion, and yearly thereafter, did not show any statistically significant changes. The animals maintained their usual appetite and body weight increased normally. Each animal responded to l-DOPA methyl ester with decreased parkinsonian signs and symptoms and increased contralateral turning. In contrast, after control vehicle administration, the animals continued to have the same parkinsonian signs and predominant ipsilateral turns. In three of the five monkeys, contralateral turns after vehicle significantly increased after 6-8 years. Unilateral intracarotid MPTP induced asymmetric motor behavior that remained stable after 6-8 years. Animals that showed an increased frequency of contralateral circling after control vehicle showed a decrease in contralateral turns after l-DOPA methyl ester, suggesting neuroplastic changes over the years.
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, 48109-0632, USA.
M E
ME
Emborg-Knott
E F
EF
Domino
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology; D002339:Carotid Arteries; D015259:Dopamine Agents / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D007261:Infusions, Intra-Arterial; D007980:Levodopa / Q000031:analogs & derivatives / Q000494:pharmacology; D020267:MPTP Poisoning; D008254:Macaca nemestrina; D009043:Motor Activity / Q000187:drug effects; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D012399:Rotation
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007980:Levodopa; C035420:levodopa methyl ester