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Early modulation by the dopamine D 4 receptor of morphine‐induced changes in the opioid peptide systems in the rat caudate putamen
Author(s) -
Gago Belén,
Fuxe Kjell,
Brené Stefan,
DíazCabiale Zaida,
ReinaSánchez María Dolores,
SuárezBoomgaard Diana,
RoalesBuján Ruth,
ValderramaCarvajal Alejandra,
Calle Adelaida,
Rivera Alicia
Publication year - 2013
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23277
Subject(s) - dynorphin , opioid , enkephalin , opioid peptide , chemistry , endocrinology , medicine , dopamine , receptor , creb , opioid receptor , morphine , pharmacology , biology , transcription factor , biochemistry , gene
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 D 4 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 D 4 receptors. The current results present evidence of functional D 4 –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. © 2013 Wiley Periodicals, Inc.