[3H]DPDPE binding to delta opioid receptors in the rat mesocorticolimbic and nigrostriatal pathways is transiently increased by acute ethanol administration.
Dopaminergic transmission in the mesolimbic and nigrostriatal pathways plays a key role in the reinforcement mechanisms and brain sensitivity to ethanol, respectively. Ethanol reinforcement and high alcohol drinking behaviour have been postulated to be partially mediated by a neurobiological mechanism involving the ethanol-induced activation of the endogenous opioid system. Activation of opioid neural pathways by ethanol may include alterations in the processing, release and/or the receptor binding of opioid peptides. The aim of this work was to investigate the effects of acute ethanol administration on delta opioid receptors in the rat mesocortical, meso-accumbens and nigrostriatal pathways by quantitative receptor autoradiography, using [(3)H] (2-D-penicillamine, 5-D-penicillamine)-enkephalin as radioligand. A significant increase in [(3)H] (2-D-penicillamine, 5-D-penicillamine)-enkephalin binding was observed in the substantia nigra pars reticulata 1 h after ethanol treatment. Two hours after drug exposure, ligand binding was significantly increased in the frontal and prefrontal cortices, the core and shell regions of the nucleus accumbens, and in the anterior-medial and medial-posterior regions of the caudate-putamen. In contrast, ligand binding was significantly decreased in the posterior region of the caudate-putamen 30 min after ethanol administration. The observed effects may reflect ethanol-induced changes in ligand binding affinity and/or in receptor density. Our results suggest that transitory changes in delta opioid receptors with different kinetic patterns may be involved in ethanol reinforcement and brain sensitivity to the drug. Ethanol-induced delta receptor up- and down-regulation mechanisms may participate in modulation of dopaminergic transmission in the mesocorticolimbic and nigrostriatal pathways.
Méndez
Milagros
M
Instituto Nacional de Psiquiatría Ramón de la Fuente, Subdirección de Investigaciones Clínicas, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., México. ubach@imp.edu.mx
Morales-Mulia
Marcela
M
Leriche
Mariana
M
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D008032:Limbic System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D000701:Analgesics, Opioid; D002492:Central Nervous System Depressants; D017465:Receptors, Opioid, delta; D014316:Tritium; D000431:Ethanol; D020881:Enkephalin, D-Penicillamine (2,5)-