Dopamine D(4) receptor activation decreases the expression of mu-opioid receptors in the rat striatum.
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 mu-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.
Gago
Belén
B
Department of Cell Biology, School of Science, University of Málaga, 29071 Málaga, Spain.
Fuxe
Kjell
K
Agnati
Luigi
L
Peñafiel
Antonio
A
De La Calle
Adelaida
A
Rivera
Alicia
A
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050638:Receptors, Dopamine D4 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013997:Time Factors
C099630:3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridine; D001549:Benzamides; D018491:Dopamine Agonists; C477501:N-((4-(2-cyanophenyl)-1-piperazinyl)methyl)-3-methylbenzamide; D010879:Piperazines; D011725:Pyridines; D011758:Pyrroles; D017450:Receptors, Opioid, mu; D050638:Receptors, Dopamine D4