title: Functional mu opioid receptors are expressed in cholinergic interneurons of the rat dorsal striatum: territorial specificity and diurnal variation.
abstract: Striatal cholinergic interneurons play a crucial role in the control of movement as well as in motivational and learning aspects of behaviour. Neuropeptides regulate striatal cholinergic transmission and particularly activation of mu opioid receptor (MOR) inhibits acetylcholine (ACh) release in the dorsal striatum. In the present study we investigated whether this cholinergic transmission could be modulated by an enkephalin/MOR direct process. We show that mRNA and protein of MORs are expressed by cholinergic interneurons in the limbic/prefrontal territory but not by those in the sensorimotor territory of the dorsal striatum. These MORs are functional because potassium-evoked release of ACh from striatal synaptosomes was dose-dependently reduced by a selective MOR agonist, this effect being suppressed by a MOR antagonist. The MOR regulation of cholinergic interneurons presented a diurnal variation. (i) The percentage of cholinergic interneurons containing MORs that was 32% at the beginning of the light period (morning) increased to 80% in the afternoon. (ii) The MOR-mediated inhibition of synaptosomal ACh release was higher in the afternoon than in the morning. (iii) While preproenkephalin mRNA levels remained stable, enkephalin tissue content was the lowest (-32%) in the afternoon when the spontaneous (+35%) and the N-methyl-d-aspartate-evoked (+140%) releases of enkephalin (from microsuperfused slices) were the highest. Therefore, by acting on MORs present on cholinergic interneurons, endogenously released enkephalin reduces ACh release. This direct enkephalin/MOR regulation of cholinergic transmission that operates only in the limbic/prefrontal territory of the dorsal striatum might contribute to information processing in fronto-cortico-basal ganglia circuits.
authors: INSERM U667 Collège de France, 11 place Marcelin Berthelot, 75231 Paris Cedex 05, France.
authors: Maritza
authors: M
authors: Jabourian
authors: Laurent
authors: L
authors: Venance
authors: Sylvie
authors: S
authors: Bourgoin
authors: Sylvie
authors: S
authors: Ozon
authors: Sylvie
authors: S
authors: Pérez
authors: Gérard
authors: G
authors: Godeheu
authors: Jacques
authors: J
authors: Glowinski
authors: Marie-Louise
authors: ML
authors: Kemel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007395:Interneurons / Q000145:classification / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives; D009292:Narcotic Antagonists; D018408:Patch-Clamp Techniques / Q000379:methods; D011188:Potassium / Q000494:pharmacology; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D009292:Narcotic Antagonists; D011498:Protein Precursors; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; D016202:N-Methylaspartate; C024524:beta-funaltrexamine; C033660:preproenkephalin; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine; D011188:Potassium