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

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

Field: Disorders of the nervous system

Authors: Andersson, Malin
Johansson, Pia
Cenci, Angela

Address of presenting
author: Avd Neurobiologi, Wallenberg Neurocenter, Sölvegatan 17, S-223 62 Lund

E-mail: Malin.Andersson@mphy.lu.se

Phone: 046-2220555

Fax: 046-2220561

Text of abstract: Opioid receptor-binding autoradiography was used as a tool to map sites of altered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Unilaterally 6-hydroxydopamine lesioned rats received single daily injections of L-DOPA, which caused about half of them to develop abnormal involuntary movements (AIMs) on the side of the body contralateral to the lesion. Lesion-only controls received daily injections of saline. Autoradiographic analysis of opioid binding sites was carried out in the caudate-putamen (CPu), the overlying primary motor area and premotor-cingulate cortex, the globus pallidus (GP) and the substantia nigra (SN). Both a non-selective opioid ligand ([3H]diprenorphine), and specific delta, kappa or mu ligands were used.
Correlations between AIM scores and basal ganglia levels of opioid binding densities were found using kappa and mu but not delta ligands. Compared to the non-dyskinetic cases, dyskinetic rats showed markedly reduced levels of kappa radioligand binding in both the SN and CPu on the lesioned side, and this was related to an enhanced striatal expression of opioid precursor mRNA. On both sides of the cortex, levels of delta and mu radioligand binding were increased in the dyskinetic group compared with the non-dyskinetic one, but kappa binding density was specifically elevated in the non-dyskinetic cases, and was negatively correlated with the rats´ AIM scores.
Our results demonstrate that chronic L-DOPA treatment produces widespread alterations in brain opioid transmission which are both structure and receptor type-specific, and conditioned by the presence or absence of dyskinetic motor effects.

Keywords: Parkinson, basal ganglia, dyskinesia, opioid

	Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of L-DOPA-induced dyskinesia
Field:	Disorders of the nervous system
Authors:	Andersson, Malin Johansson, Pia Cenci, Angela
Address of presenting author:	Avd Neurobiologi, Wallenberg Neurocenter, Sölvegatan 17, S-223 62 Lund
E-mail:	Malin.Andersson@mphy.lu.se
Phone:	046-2220555
Fax:	046-2220561
Text of abstract:	Opioid receptor-binding autoradiography was used as a tool to map sites of altered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Unilaterally 6-hydroxydopamine lesioned rats received single daily injections of L-DOPA, which caused about half of them to develop abnormal involuntary movements (AIMs) on the side of the body contralateral to the lesion. Lesion-only controls received daily injections of saline. Autoradiographic analysis of opioid binding sites was carried out in the caudate-putamen (CPu), the overlying primary motor area and premotor-cingulate cortex, the globus pallidus (GP) and the substantia nigra (SN). Both a non-selective opioid ligand ([3H]diprenorphine), and specific delta, kappa or mu ligands were used. Correlations between AIM scores and basal ganglia levels of opioid binding densities were found using kappa and mu but not delta ligands. Compared to the non-dyskinetic cases, dyskinetic rats showed markedly reduced levels of kappa radioligand binding in both the SN and CPu on the lesioned side, and this was related to an enhanced striatal expression of opioid precursor mRNA. On both sides of the cortex, levels of delta and mu radioligand binding were increased in the dyskinetic group compared with the non-dyskinetic one, but kappa binding density was specifically elevated in the non-dyskinetic cases, and was negatively correlated with the rats´ AIM scores. Our results demonstrate that chronic L-DOPA treatment produces widespread alterations in brain opioid transmission which are both structure and receptor type-specific, and conditioned by the presence or absence of dyskinetic motor effects.

Keywords:	Parkinson, basal ganglia, dyskinesia, opioid

Index

Created 2000-02-14

Department of Physiological Sciences, Lund University

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