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The role of opioid receptor agonists and antagonists in the treatment of Parkinson’s disease

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Abstract

A possible mechanism underlying the role of opioids in the treatment of Parkinson’s disease and L-dopa-induced dyskinesias is suggested. This role is based on the reorganization of neuronal firing in the motor cortico-basal ganglia-thalamocortical loop as a consequence of opioid-mediated LTD induction in the spiny cells of the input basal ganglia nucleus, striatum. Analysis of existing data allowed us to propose that the striatonigral cells in the striosomes and matrix that release dynorphin mainly express μ and κ opioid receptors, respectively, whereas striatopallidal cells that release enkephalin express δ opioid receptors. The proposed mechanism implies that in addition to agonists of dopamine receptors and antagonists of muscarinic receptors, μ and δ receptor agonists and/or κ receptor antagonists might alleviate the symptoms of Parkinson’s disease and allow recovery of locomotor activity. Recurrent collaterals of striatal spiny cells innervating their dendrites and bodies, as well as those of striatal cholinergic interneurons, form negative feedback loops that allow opioid peptides and substance P to regulate and stabilize striatal output pathways. Therefore, in the absence of activation of the D2 and D1 receptors on striatal spiny cells, increased enkephalin concentration and decreased dynorphin and substance P level promote the suppression of acetylcholine release (due to modulation of cholinergic interneuron firing through κ opioid and NK receptors), thus reducing the impact of a dopamine deficit on basal ganglia functioning. Opposing changes in opioid concentrations, due to L-dopa treatment and reorganization of activity in the same neuronal loops, may reduce dyskinesias.

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Abbreviations

BG:

basal ganglia

LID:

L-dopa-induced dyskinesias

LTD:

long-term depression

LTP:

long-term potentiation

SNr:

substantia nigra pars reticulata

GPe and GPi:

external and internal parts of the globus pallidus

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  1. Institute of Higher Nervous Activity and Neurophysiology of the Russian Academy of Sciences, ul. Butlerova 5a, Moscow, 117485, Russia

    I. G. Silkis

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Silkis, I.G. The role of opioid receptor agonists and antagonists in the treatment of Parkinson’s disease. Neurochem. J. 1, 281–287 (2007). https://doi.org/10.1134/S1819712407040034

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  • DOI: https://doi.org/10.1134/S1819712407040034

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