Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of L-DOPA-induced dyskinesia

Opioid receptor-binding autoradiography was used as a way to map sites of a ltered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Rat s with unilateral B-hydroxydopamine lesions of the nigrostriatal pathways s ustained a 3-week treatment with L-DOPA (6 mg/kg/day, combined with 12 mg/k g/day benserazide), causing about half of them to develop dyskinetic-like m ovements on the side of the body contralateral to the lesion. Autoradiograp hic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nig ra (SN), the primary motor area, and the premotor-cingulate cortex. The dop amine-denervating lesion alone caused an ipsitateral reduction in opioid ra dioligand binding in the Cpu, GP, and SN, but not in the cerebral cortex. C hronic L-DOPA treatment affected opioid receptor binding in both the basal ganglia and the cerebral cortex, producing changes that were both structure - and receptor-type specific, and closely related to the motor response eli cited by the treatment. In the basal ganglia, the most clear-cut difference s between dyskinetic and nondyskinetic rats pertained to kappa opioid sites . On the lesioned side, both striatal and nigral levels of kappa binding de nsities were significantly lower in the dyskinetic group, showing a negativ e correlation with the rats' dyskinesia scores on one hand and with the str iatal expression of opioid precursor mRNAs on the other hand. In the cerebr al cortex, levels of mu and delta binding site densities were bilaterally e levated in the dyskinetic group, whereas kappa radioligand binding was spec ifically increased in the nondyskinetic cases and showed a negative correla tion with the rats' dyskinesia scores. These data demonstrate that bilatera l changes in cortical opioid transmission are closely associated with L-DOP A-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and non dyskinetic animals often show opposite changes in opioid radioligand bindin g suggests that the motor response to L-DOPA is determined, at least in par t, by compensatory adjustments of brain opioid receptors. (C) 2001 Academic Press