title: Impact of 6-hydroxydopamine lesions and cocaine exposure on mu-opioid receptor expression and regulation of cholinergic transmission in the limbic-prefrontal territory of the rat dorsal striatum.
abstract: Information processing within the striatum is regulated by local circuits involving dopamine, cholinergic interneurons and neuropeptides released by recurrent collaterals of striatal output neurons. In the limbic-prefrontal territory of the dorsal striatum, enkephalin inhibits the NMDA-evoked release of acetylcholine directly through micro-opioid receptors (MORs) located on cholinergic interneurons and indirectly through MORs of output neurons of striosomes. In this territory, we investigated the consequence of changes in dopamine transmission, bilateral 6-hydroxydopamine-induced degeneration of striatal dopaminergic innervation or cocaine (acute and chronic) exposure on (i) MOR expression in both cholinergic interneurons and output neurons of striosomes, and (ii) the direct and indirect enkephalin-MOR regulations of the NMDA-evoked release of acetylcholine. Expression of MORs in cholinergic interneurons was preserved after 6-hydroxydopamine and down-regulated after cocaine treatments. Accordingly, the direct enkephalin-MOR control of acetylcholine release was preserved after 6-hydroxydopamine treatment and lost after cocaine exposure. Expression of MORs in output neurons of striosomes was down-regulated in the 6-hydroxydopamine situation and either preserved or up-regulated after acute or chronic cocaine exposure, respectively. Accordingly, the indirect enkephalin-MOR control of acetylcholine release disappeared in the 6-hydroxydopamine situation but surprisingly, despite preservation of MORs in striosomes, disappeared after cocaine treatment. Showing that MORs of striosomes are still functional in this situation, the MOR agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin inhibited the NMDA-evoked release of acetylcholine after cocaine exposure. Therefore, alteration in the regulation of cholinergic transmission by the enkephalin-MOR system might play a major role in the motivational and cognitive disorders associated with dopamine dysfunctions in fronto-cortico-basal ganglia circuits.
authors.affiliation: INSERM U667, Collège de France, 11 place Marcelin Berthelot, F-75231 Paris Cedex 05, France.
authors.forename: Maritza
authors.initials: M
authors.lastname: Jabourian
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pérez
authors.forename: Pascal
authors.initials: P
authors.lastname: Ezan
authors.forename: Jacques
authors.initials: J
authors.lastname: Glowinski
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Deniau
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Kemel
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D008297:Male; D008959:Models, Neurological; D016202:N-Methylaspartate / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D018690:Excitatory Amino Acid Agonists; D017450:Receptors, Opioid, mu; C512611:enkephalin, Ala(2)-MePhe(4)-GlyNH2(5)-; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016202:N-Methylaspartate; D016627:Oxidopamine; D003042:Cocaine; D000109:Acetylcholine