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: 4.7). 05/2012; 236(2):339-50. DOI: 10.1016/j.expneurol.2012.04.017
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.
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ABSTRACT: Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Our knowledge of DOR function has enormously progressed from in vivo studies using pharmacological tools and genetic approaches. The important role of this receptor in reducing chronic pain has been extensively overviewed; therefore this review focuses on facets of delta receptor activity relevant to psychiatric and other neurological disorders. Beneficial effects of DOR agonists are now well established in the context of emotional responses and mood disorders. DOR activation also regulates drug reward, inhibitory controls and learning processes, but whether delta compounds may represent useful drugs in the treatment of drug abuse remains open. Epileptogenic and locomotor-stimulating effects of delta agonists appear drug-dependent, and the possibility of biased agonism at DOR for these effects is worthwhile further investigations to increase benefit/risk ratio of delta therapies. Neuroprotective effects of DOR activity represent a forthcoming research area. Future developments in DOR research will benefit from in-depth investigations of DOR function at cellular and circuit levels.Pharmacology [?] Therapeutics 06/2013; 140(1). DOI:10.1016/j.pharmthera.2013.06.003 · 9.72 Impact Factor
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ABSTRACT: Glutamate is known to cause the release of dopamine through a Ca(2+)-sensitive mechanism that involves activation of NMDA ionotropic glutamate receptors. In the current study, we tested the hypothesis that the delta opioid agonist SNC80 acts indirectly, via the glutamatergic system, to enhance both amphetamine-stimulated dopamine efflux from striatal preparations and amphetamine-stimulated locomotor activity. SNC80 increased extracellular glutamate content, which was accompanied by a concurrent decrease in GABA levels. Inhibition of NMDA signaling with the selective antagonist MK801 blocked the enhancement of both amphetamine-induced dopamine efflux and hyperlocomotion observed with SNC80 pretreatment. Addition of exogenous glutamate also potentiated amphetamine-stimulated dopamine efflux in a Mg(2+)- and MK801-sensitive manner. After removal of Mg(2+) to relieve the ion conductance inhibition of NMDA receptors, SNC80 both elicited dopamine release alone and produced a greater enhancement of amphetamine-evoked dopamine efflux. The action of SNC80 to enhance amphetamine-evoked dopamine efflux was mimicked by the GABAB antagonist 2-hydroxysaclofen. These cumulative findings suggest SNC80 modulates amphetamine-stimulated dopamine efflux through an intra-striatal mechanism involving inhibition of GABA transmission leading to the local release of glutamate followed by subsequent activation of NMDA receptors.Neuropharmacology 09/2013; 77. DOI:10.1016/j.neuropharm.2013.08.027 · 5.11 Impact Factor
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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; 50. DOI:10.1016/j.peptides.2013.10.001 · 2.62 Impact Factor
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