Influence of corticostriatal δ-opioid receptors on abnormal involuntary movements induced by L-DOPA in hemiparkinsonian rats.

Experimental Neuropsychopharmacology Laboratory (EA 4359), University and Hospital Institute of Biomedical Research, University of Rouen, IFR23, 76183 Rouen, France.
Experimental Neurology (Impact Factor: 4.62). 05/2012; 236(2):339-50. DOI: 10.1016/j.expneurol.2012.04.017
Source: PubMed

ABSTRACT Chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment of Parkinson's disease induces in time numerous side effects, such as abnormal involuntary movements called L-DOPA-induced dyskinesias (LIDs). An involvement of glutamate transmission, dopamine transmission and opioid transmission in striatal output pathways has been hypothesized for the induction of LIDs. Interestingly, our previous experiments indicated that some striatal δ-opioid receptors are located on terminals of glutamatergic corticostriatal neurons and that stimulation of these receptors modulates the release of glutamate and dopamine. The present study was performed to test the involvement of δ-opioid receptors, and more precisely of those located on corticostriatal neurons, in abnormal involuntary movements induced by L-DOPA in hemiparkinsonian rats. The effects of a selective agonist, [D-Pen(2), D-Pen(5)]-enkephalin (DPDPE) and a selective antagonist (naltrindole) of δ-opioid receptors on LIDs were investigated in animals submitted or not to a corticostriatal deafferentation. Our results indicate that DPDPE and naltrindole respectively enhanced and reduced LIDs in animals in which the ipsilateral cortex was preserved intact. However, the lesion of the ipsilateral cortex prevented the stimulant effect of DPDPE on LIDs. The [(3)H]-DPDPE binding to striatal membranes prepared from the whole striatum was also studied. A significant increase in density of δ-opioid receptors was found in the striatum of dyskinetic animals as compared to non-dyskinetic animals but this difference was abolished by the corticostriatal deafferentation. These results indicate that δ-opioid transmission modulates the expression of LIDs in rodents and suggest that the δ-opioid receptors involved in this effect are located on terminals of corticostriatal neurons.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Parkinson's disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.
    Journal of the American Society for Experimental NeuroTherapeutics 10/2013; · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper is the thirty-fifth consecutive installment of the annual review of research concerning the endogenous opioid system. It summarizes papers published during 2012 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides, opioid receptors, opioid agonists and opioid antagonists. The particular topics that continue to be covered include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors related to behavior (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology (Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).
    Peptides 10/2013; · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Levodopa-induced dyskinesias (LIDs) and graft-induced dyskinesias (GIDs) are serious and common complications of Parkinson's disease (PD) management following chronic treatment with levodopa or intrastriatal transplantation with dopamine-rich foetal ventral mesencephalic tissue, respectively. Positron emission tomography (PET) molecular imaging provides a powerful in vivo tool that has been employed over the past 20 years for the elucidation of mechanisms underlying the development of LIDs and GIDs in PD patients. PET used together with radioligands tagging molecular targets has allowed the functional investigation of several systems in the brain including the dopaminergic, serotonergic, glutamatergic, opioid, endocannabinoid, noradrenergic and cholinergic systems. In this article the role of PET imaging in unveiling pathophysiological mechanisms underlying the development of LIDs and GIDs in PD patients is reviewed.
    European Journal of Neurology 01/2014; · 3.85 Impact Factor