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Int. J. Mol. Sci. 2014, 15(1), 1481-1498; doi:10.3390/ijms15011481
Article

Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen

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Received: 30 November 2013; in revised form: 8 January 2014 / Accepted: 13 January 2014 / Published: 21 January 2014
(This article belongs to the collection G Protein-Coupled Receptor Signaling and Regulation)
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Abstract: 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 Bmax values to the same degree as seen after continuous morphine treatment. Thus, in spite of the fact that both receptors can be coupled to Gi/0 protein, the present results give support for the existence of antagonistic functional D4R-MOR receptor-receptor interactions in the adaptive changes occurring in MOR of striosomes on continuous administration of morphine.
Keywords: morphine; PD168,077; µ opioid receptor; dopamine D4 receptor; G proteins; caudate putamen; striosomes; addiction morphine; PD168,077; µ opioid receptor; dopamine D4 receptor; G proteins; caudate putamen; striosomes; addiction
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Suárez-Boomgaard, D.; Gago, B.; Valderrama-Carvajal, A.; Roales-Buján, R.; Craenenbroeck, K.V.; Duchou, J.; Borroto-Escuela, D.O.; Medina-Luque, J.; de la Calle, A.; Fuxe, K.; Rivera, A. Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen. Int. J. Mol. Sci. 2014, 15, 1481-1498.

AMA Style

Suárez-Boomgaard D, Gago B, Valderrama-Carvajal A, Roales-Buján R, Craenenbroeck KV, Duchou J, Borroto-Escuela DO, Medina-Luque J, de la Calle A, Fuxe K, Rivera A. Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen. International Journal of Molecular Sciences. 2014; 15(1):1481-1498.

Chicago/Turabian Style

Suárez-Boomgaard, Diana; Gago, Belén; Valderrama-Carvajal, Alejandra; Roales-Buján, Ruth; Craenenbroeck, Kathleen V.; Duchou, Jolien; Borroto-Escuela, Dasiel O.; Medina-Luque, José; de la Calle, Adelaida; Fuxe, Kjell; Rivera, Alicia. 2014. "Dopamine D4 Receptor Counteracts Morphine-Induced Changes in µ Opioid Receptor Signaling in the Striosomes of the Rat Caudate Putamen." Int. J. Mol. Sci. 15, no. 1: 1481-1498.



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