Rest tremor in rhesus monkeys with MPTP-induced parkinsonism.
Rest tremor (RTr) is a typical feature of Parkinson's diseases (PD). Animal models of PD presenting with RTr are indispensable for understanding the pathophysiology of human RTr and the development of new therapeutic agents. In this report we studied the occurrence of tremor on rhesus monkeys rendered parkinsonian by an intracarotid (ICA) infusion followed by 2-4 iv. doses of n-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The animals' parkinsonism was assessed using a rating scale, activity monitors and a novel tremor monitor. The animals manifested bilateral parkinsonism with more severe clinical signs on the side of the body contralateral to the ICA infusion. The RTr in these animals had a mean peak frequency of 7.9 Hz (S.E.: 0.12), and a mean amplitude of 5.1/d/s/rtz (S.E.: 0.69). Substantial reduction in RTr amplitude (80.4%) was observed after oral L-DOPA administration. Our results suggest that: 1) RTr is present after the combined administration of ICA and iv. MPTP. 2) The mean RTr frequency in rhesus monkeys may be higher than in parkinsonian patients. However, as in PD, RTr frequency in the monkey was maintained within a narrow band width. 3) As in PD, L-DOPA administration to MPTP-treated monkeys reduced the amplitude of RTr and improved the parkinsonian features. Monitoring and quantifying the RTr in the MPTP-parkinsonian monkeys provide an objective, non invasive way to measure the outcome of therapeutic interventions and, further support the concept that loss of dopaminergic innervation contributes to the occurrence of RTr.
Emborg
Marina E
ME
Department of Neurological Sciences and Center for Brain Repair, Rush University, Chicago, IL 60612, USA. memborg@rush.edu
Tetrud
James W
JW
Moirano
Jeff
J
McLaughlin
William W
WW
Bankiewicz
Krys S
KS
D000818:Animals; D005260:Female; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced* / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D014202:Tremor / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*
D007980:Levodopa