New Parallels Between Parkinson’s Disease and MPTP-Induced Parkinsonism in the Monkey
Despite the very significant advances that have been made in the treatment of Parkinson’s disease with the introduction of levodopa therapy the management of the condition still presents major problems to the clinician. While some patients undoubtedly have a benign, relatively non-progressive type of the disorder, others develop response fluctuations, the ‘on-off’ phenomenon, peak-dose dyskinesias related to levodopa medication or become unresponsive to treatment. It has been suggested that these complications may be related to prolonged levodopa medication (Rajput et al., 1984 and Melamed, 1986) and the concept of delayed treatment and wider use of dopamine agonists has been proposed. Insight into their aetiology may come fron the introduction of PET scanning as a non-invasive method of studying cerebral metabolism and neurotransmitter receptor binding but a non-human primate model of Parkinson’s disease still remains an attractive and important development. Such a model has ironically presented itself in humans with the discovery of a parkinsonian syndrome in drug addicts who have received l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) produced during the synthesis of “designer drugs”. MPTP has been administered to monkeys and found to produce a very realistic parkinsonian syndrome but so far it has not been confirmed that the histological changes are similar in appearance and distribution to those found in Parkinson’s disease. Furthermore, it is not known whether the problems of levodopa administration are also encountered in the animal model.
KeywordsNucleus Accumbens Caudate Nucleus Anterior Commissure Levodopa Therapy Parkinsonian Syndrome
Unable to display preview. Download preview PDF.
- Burns, R.S., Chiueh, C.C., Markey, S.P., Ebert, M.H., Jacobowitz, D.M. and Kopin, I.J., 1983. A primate model of parkinsonism: selective destruction of dopaminergic neurones in the pars compacta of the substantia nigra by N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Proc. Natl. Acad. Sci. USA, 80: 4546–4550.PubMedCrossRefGoogle Scholar
- Joyce, J.N., Marshall, J.F., Bankiewicz, K.S., Kopin I.J. and Jacobowitz D.M., 1986. Hemiparkinsonism in a monkey after unilateral internal carotid artery infusion of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) is associated with regional ipsilateral changes in striatal dopamine D-2 receptor density. Brain Res.; 382: 360–364.PubMedCrossRefGoogle Scholar
- Rinne, U., Koskinen, V. and Lonnberg, P., 1980. Neurotransmitter receptors in the parkinsonian brain. in Rinne, U., Klingler, M. and Stamm, G. (eds): Parkinson’s Disease — Current Progress, Problems and Management, New York, Elsevier/ North-Holland Biomedical Press: 93–107.Google Scholar
- Rinne, U., Rinne J.O. and Rinne, J.K., 1983. Brain receptor changes in Parkinson’s disease in relation to the disease process and treatment. J. Neural. Transm. (suppl), 18: 279–286.Google Scholar
- Winkler, M., Berl, S., Whetsell, W. and Yahr, M., 1980. Spiroperidol binding in the human caudate nucleus. J. Neural. Transm.(suppl) 16: 45–51.Google Scholar