title: Early modulation by the dopamine D4 receptor of morphine-induced changes in the opioid peptide systems in the rat caudate putamen.
abstract: The peptides dynorphin and enkephalin modulate many physiological processes, such as motor activity and the control of mood and motivation. Their expression in the caudate putamen (CPu) is regulated by dopamine and opioid receptors. The current work was designed to explore the early effects of the acute activation of D4 and/or μ opioid receptors by the agonists PD168,077 and morphine, respectively, on the regulation of the expression of these opioid peptides in the rat CPu, on transcription factors linked to them, and on the expression of μ opioid receptors. In situ hybridization experiments showed that acute treatment with morphine (10 mg/kg) decreased both enkephalin and dynorphin mRNA levels in the CPu after 30 min, but PD168,077 (1 mg/kg) did not modify their expression. Coadministration of the two agonists demonstrated that PD168,077 counteracted the morphine-induced changes and even increased enkephalin mRNA levels. The immunohistochemistry studies showed that morphine administration also increased striatal μ opioid receptor immunoreactivity but reduced P-CREB expression, effects that were blocked by the PD168,077-induced activation of D4 receptors. The current results present evidence of functional D4 -μ opioid receptor interactions, with consequences for the opioid peptide mRNA levels in the rat CPu, contributing to the integration of DA and opioid peptide signaling.
authors.affiliation: Department of Cell Biology, School of Science, University of Málaga, Málaga, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Gago
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.forename: Stefan
authors.initials: S
authors.lastname: Brené
authors.forename: Zaida
authors.initials: Z
authors.lastname: Díaz-Cabiale
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Reina-Sánchez
authors.forename: Diana
authors.initials: D
authors.lastname: Suárez-Boomgaard
authors.forename: Ruth
authors.initials: R
authors.lastname: Roales-Buján
authors.forename: Alejandra
authors.initials: A
authors.lastname: Valderrama-Carvajal
authors.forename: Adelaida
authors.initials: A
authors.lastname: de la Calle
authors.forename: Alicia
authors.initials: A
authors.lastname: Rivera
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004399:Dynorphins / Q000096:biosynthesis; D004745:Enkephalins / Q000096:biosynthesis; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D018847:Opioid Peptides / Q000096:biosynthesis*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D018847:Opioid Peptides; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D050638:Receptors, Dopamine D4; D004399:Dynorphins; D009020:Morphine
keywords: D4/μ opioid receptors interactions; opioid peptides; striatum; transcription factors