Speculations on the Molecular Mechanisms Underlying Dopamine Agonist-Induced Dyskinesias in Parkinsonism
Long-term treatment of Parkinson’s disease with dopamine-replacing agents fre-quently results in the appearance of debilitating dyskinetic side-effects. The neural mechanisms underlying these so-called dopamine agonist-induced dyskinesias remain unclear. This chapter summarises some of our recent molecular data, obtained in the 6-hydroxydopaminelesioned rat model of Parkinson’s disease, that suggest a role for both enkephalin and dynorphin in the generation of the symptoms of dopamine agonist-induced dyskinesias.
KeywordsGlobus Pallidus Subthalamic Nucleus Kappa Opioid Receptor Dopamine Replacement Therapy Lesion Striatum
Unable to display preview. Download preview PDF.
- Greenamyre, J.T., 1993, Glutamate-dopamine interactions in the basal ganglia: relationship to Parkinson’s disease, J. Neurotransm. 91: 255–269.Google Scholar
- Jongen-Rêlo, A.L., Docter, G.J., Jonker, A.J., Vreugdenhil, E., Groenewegen, H.J. and Voorn, P., 1994, Differential effects of dopamine depletion on the binding and mRNA levels of dopamine receptors in the shell and core of the rat nucleus accumbens, Mol. Brain Res. 25: 333–343.PubMedCrossRefGoogle Scholar
- Llorens-Cortes, C., Van Amsterdam, J.G.C., Giros, B., Qauch, T.T. and Schwarz, J.C., 1990, Enkephalin biosynthesis and release in mouse striatum are inhibited by GABA receptor stimulation: compared changes in preproenkephalin mRNA and Tyr-Gly-Gly levels, Mol. Brain Res. 8: 227–233.PubMedCrossRefGoogle Scholar
- Maneuf, Y.P., Mitchell, I.J., Crossman, A.R., Woodruff, G.N. and Brotchie, J.M., 1995, Functional implications of kappa opioid receptor-mediated modulation of glutamate transmission in the output regions of the basal ganglia in rodent and primate models of Parkinson’s disease, Brain Res. 683: 102–108.PubMedCrossRefGoogle Scholar
- Mitchell, I.J., Clarke, C.E., Boyce, S., Robertson, R.G., Peggs, D., Sambrook, M.A. and Crossman, A.R., 1989a, Neural mechanisms underlying parkinsonian symptoms based upon regional uptake of 2-deoxyglucose in monkeys exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neuroscience 32: 213–226.PubMedCrossRefGoogle Scholar
- Paxinos, G. and Watson, C., 1985, The Rat Brain in Stereotaxic Coordinates, Academic Press, New York.Google Scholar
- Voorn, P., Docter, G.J., Jongen-Rêlo, A.L. and Jonker, A.J., 1994, Rostrocaudal sub-regional differences in the response of enkephalin, dynorphin and substance P synthesis in rat nucleus accumbens to dopamine depletion, Eur. J. Neurosci. 486-496.Google Scholar