International Journal of Molecular Sciences | |
Dopamine D4 Receptor Counteracts Morphine-Induced Changes in μ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen | |
Diana Suárez-Boomgaard1  Belén Gago3  Alejandra Valderrama-Carvajal1  Ruth Roales-Buján1  Kathleen Van Craenenbroeck4  Jolien Duchou4  Dasiel O. Borroto-Escuela2  José Medina-Luque1  Adelaida de la Calle1  Kjell Fuxe2  | |
[1] Department of Cell Biology, School of Science, University of Málaga, 29071 Málaga, Spain; E-Mails:;Department of Neuroscience, Karolinska Institutet, Retzius väg 8, 17177 Stockholm, Sweden; E-Mails:;Department of Neuroscience, Biodonostia Institute, 20014 San Sebastián, Spain; E-Mail:;Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Ghent University-Gent, 9000 Ghent, Belgium; E-Mails: | |
关键词: morphine; PD168; 077; μ opioid receptor; dopamine D4 receptor; G proteins; caudate putamen; striosomes; addiction; | |
DOI : 10.3390/ijms15011481 | |
来源: mdpi | |
【 摘 要 】
The mu opioid receptor (MOR) is critical in mediating morphine analgesia. However, prolonged exposure to morphine induces adaptive changes in this receptor leading to the development of tolerance and addiction. In the present work we have studied whether the continuous administration of morphine induces changes in MOR protein levels, its pharmacological profile, and MOR-mediated G-protein activation in the striosomal compartment of the rat CPu, by using immunohistochemistry and receptor and DAMGO-stimulated [35S]GTPγS autoradiography. MOR immunoreactivity, agonist binding density and its coupling to G proteins are up-regulated in the striosomes by continuous morphine treatment in the absence of changes in enkephalin and dynorphin mRNA levels. In addition, co-treatment of morphine with the dopamine D4 receptor (D4R) agonist PD168,077 fully counteracts these adaptive changes in MOR, in spite of the fact that continuous PD168,077 treatment increases the [3H]DAMGO
【 授权许可】
CC BY
© 2014 by the authors; licensee MDPI, Basel, Switzerland
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