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Dopamine D 4 receptor activation decreases the expression of μ‐opioid receptors in the rat striatum
Author(s) -
Gago Belén,
Fuxe Kjell,
Agnati Luigi,
Peñafiel Antonio,
De La Calle Adelaida,
Rivera Alicia
Publication year - 2007
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.21327
Subject(s) - raclopride , agonist , striatum , dopaminergic , receptor , dopamine , μ opioid receptor , ventral striatum , opioid , dopamine receptor d2 , biology , medicine , neuroscience , pharmacology , endocrinology , chemistry
Abstract The dopaminergic and opioid peptide systems interact in many nuclei of the brain. In the striatum, dopamine/opioid peptide interactions modulate locomotor and motivated behaviors as well as reward, motivational, and tolerance processes in opiate dependence. Dopamine D 4 receptors (D 4 R) and μ‐opioid receptors (MOR) are highly concentrated in the striosomes (islands) of the striatum, suggesting the existence of receptor–receptor interactions between them. In the present work we studied the role of D 4 R in modulating MOR expression in the islands by using immunohistochemistry and image analysis. The activation of D 4 R by the agonist PD168,077 (1 mg/kg) decreased MOR immunoreactivity (IR) in the striosomes 6 hours after drug treatment. MOR IR levels had recovered 12 hours later. Treatment with a D 4 R antagonist (L745,870, 1mg/kg) blocked downregulation of MOR IR, showing that the D 4 R agonist effects observed were specific. Furthermore, treatment with the D 2 /D 3 receptor agonist quinpirol (1 mg/kg) and D 2 /D 3 receptor antagonist raclopride (1 mg/kg) had no effect in MOR IR, suggesting that D 4 R is the only D2‐like receptor producing an MOR downregulation in the islands. The decreases of MOR IR in the striosomes suggest that D 4 R activation may reduce MOR signaling. Increasing evidence has demonstrated that the islands in the striatum play a critical role in habit acquisition during drug addiction. D 4 R/MOR interactions could be crucial in such processes. J. Comp. Neurol. 502:358–366, 2007. © 2007 Wiley‐Liss, Inc.