Neurochemical and pharmaco-behavioural studies on the biological basis of oral dyskinesia

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1.Oral dyskinesia is a neurological syndrome associated with aging or use of neuroleptics and drugs for Parkinson's disease. It is characterized by repetitive stereotyped oral movement. The detailed pathophysiological basis of the disorder remains unclear, but behavioural studies suggest the significance of increase in dopamine (DA) function in the striatum and nucleus accumbens for the production of repetitive jaw movements of rats. In order to investigate the biological basis of the enhancement of DA function, we focused on the mechanisms of action of (1)the intrastriatal injection of dexamphetamine on the striatal DA efflux, (2)the intraaccumbal infusion of the putative delta receptor agonist TAN-67 on the accumbal DA efflux, (3)the intraaccumbal infusion of endomorphin (EM)-2 and EM-1, the endogenous mu receptor agonists on the accumbal DA efflux and (4)the local infusion of alpha-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor on the striatal and accumbal DA efflux. The DA levels were monitored by in vivo brain microdialysis.2.The present study reveals that (1)both vesicular and cytosolic DA pools contribute to the intrastriatal injection of dexamphetamine-induced striatal DA efflux. (2)(-)-TAN-67 can generate a burst of free radicals that trigger glutamate release which ultimately activates NMDA receptors that enhance the accumbal DA levels. (3)The intraaccumbal infusion of EM-2 and EM-1 increase accumbal DA efflux by mechanisms that differ. Thus, the effects of EM-2 are not mediated via opioid receptors in contrast to the effects of EM-1 that are mediated via mu1-opioid receptors. (4)The local infusion of AMPT is a valuable tool for analyzing the role of AMPT-sensitive DA pools within a particular brain area, but it cannot be used to compare effects across different brain structures, since a fixed dose of AMPT differentially affects the nucleus accumbens and dorsal striatum.