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

Johansson, P. A.; Andersson, M.; Andersson, K. E. and Cenci, M. A. LU (2001) In Neurobiology of Disease 8(2). p.220-239
Abstract

Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with L-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in... (More)

Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with L-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but not in the cerebral cortex. Chronic 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 elicited by the treatment. In the basal ganglia, the most clear-cut differences between dyskinetic and nondyskinetic rats pertained to kappa opioid sites. On the lesioned side, both striatal and nigral levels of kappa binding densities were significantly lower in the dyskinetic group, showing a negative correlation with the rats' dyskinesia scores on one hand and with the striatal expression of opioid precursor mRNAs on the other hand. In the cerebral cortex, levels of mu and delta binding site densities were bilaterally elevated in the dyskinetic group, whereas kappa radioligand binding was specifically increased in the nondyskinetic cases and showed a negative correlation with the rats' dyskinesia scores. These data demonstrate that bilateral changes in cortical opioid transmission are closely associated with L-DOPA-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show opposite changes in opioid radioligand binding suggests that the motor response to L-DOPA is determined, at least in part, by compensatory adjustments of brain opioid receptors.

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organization
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Contribution to journal
publication status
published
subject
keywords
Dynorphin, Enkephalin, In situ hybridization, Movement disorders, Neocortex, Neuropeptides, Parkinson's disease, Striatonigral, Striatopallidal
in
Neurobiology of Disease
volume
8
issue
2
pages
20 pages
publisher
Elsevier
external identifiers
  • scopus:0035036009
ISSN
0969-9961
DOI
10.1006/nbdi.2000.0372
language
English
LU publication?
yes
id
90e29aeb-3ac9-4f3f-88d4-8689f3633925
date added to LUP
2017-04-24 13:09:02
date last changed
2018-10-21 04:46:01
@article{90e29aeb-3ac9-4f3f-88d4-8689f3633925,
  abstract     = {<p>Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of L-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with L-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but not in the cerebral cortex. Chronic 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 elicited by the treatment. In the basal ganglia, the most clear-cut differences between dyskinetic and nondyskinetic rats pertained to kappa opioid sites. On the lesioned side, both striatal and nigral levels of kappa binding densities were significantly lower in the dyskinetic group, showing a negative correlation with the rats' dyskinesia scores on one hand and with the striatal expression of opioid precursor mRNAs on the other hand. In the cerebral cortex, levels of mu and delta binding site densities were bilaterally elevated in the dyskinetic group, whereas kappa radioligand binding was specifically increased in the nondyskinetic cases and showed a negative correlation with the rats' dyskinesia scores. These data demonstrate that bilateral changes in cortical opioid transmission are closely associated with L-DOPA-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show opposite changes in opioid radioligand binding suggests that the motor response to L-DOPA is determined, at least in part, by compensatory adjustments of brain opioid receptors.</p>},
  author       = {Johansson, P. A. and Andersson, M. and Andersson, K. E. and Cenci, M. A.},
  issn         = {0969-9961},
  keyword      = {Dynorphin,Enkephalin,In situ hybridization,Movement disorders,Neocortex,Neuropeptides,Parkinson's disease,Striatonigral,Striatopallidal},
  language     = {eng},
  number       = {2},
  pages        = {220--239},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of L-DOPA-induced dyskinesia},
  url          = {http://dx.doi.org/10.1006/nbdi.2000.0372},
  volume       = {8},
  year         = {2001},
}