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The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders

The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS represents a novel integrative molecular mechanism in the plasma membrane of neurons and glial cells. It was proposed that they form the molecular basis for learning and short-and long-t...

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Autores principales: Borroto-Escuela, Dasiel O., Wydra, Karolina, Fores-Pons, Ramon, Vasudevan, Lakshmi, Romero-Fernandez, Wilber, Frankowska, Małgorzata, Ferraro, Luca, Beggiato, Sarah, Crespo-Ramirez, Minerva, Rivera, Alicia, Rocha, Luisa L., Perez de la Mora, Miguel, Stove, Christophe, Filip, Małgorzata, Fuxe, Kjell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005530/
https://www.ncbi.nlm.nih.gov/pubmed/33790790
http://dx.doi.org/10.3389/fphar.2021.627032
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author Borroto-Escuela, Dasiel O.
Wydra, Karolina
Fores-Pons, Ramon
Vasudevan, Lakshmi
Romero-Fernandez, Wilber
Frankowska, Małgorzata
Ferraro, Luca
Beggiato, Sarah
Crespo-Ramirez, Minerva
Rivera, Alicia
Rocha, Luisa L.
Perez de la Mora, Miguel
Stove, Christophe
Filip, Małgorzata
Fuxe, Kjell
author_facet Borroto-Escuela, Dasiel O.
Wydra, Karolina
Fores-Pons, Ramon
Vasudevan, Lakshmi
Romero-Fernandez, Wilber
Frankowska, Małgorzata
Ferraro, Luca
Beggiato, Sarah
Crespo-Ramirez, Minerva
Rivera, Alicia
Rocha, Luisa L.
Perez de la Mora, Miguel
Stove, Christophe
Filip, Małgorzata
Fuxe, Kjell
author_sort Borroto-Escuela, Dasiel O.
collection PubMed
description The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS represents a novel integrative molecular mechanism in the plasma membrane of neurons and glial cells. It was proposed that they form the molecular basis for learning and short-and long-term memories. This is also true for drug memories formed during the development of substance use disorders like morphine and cocaine use disorders. In cocaine use disorder it was found that irreversible A2AR-D2R complexes with an allosteric brake on D2R recognition and signaling are formed in increased densities in the ventral enkephalin positive striatal-pallidal GABA antireward neurons. In this perspective article we discuss and propose how an increase in opioid heteroreceptor complexes, containing MOR-DOR, MOR-MOR and MOR-D2R, and their balance with each other and A2AR-D2R complexes in the striatal-pallidal enkephalin positive GABA antireward neurons, may represent markers for development of morphine use disorders. We suggest that increased formation of MOR-DOR complexes takes place in the striatal-pallidal enkephalin positive GABA antireward neurons after chronic morphine treatment in part through recruitment of MOR from the MOR-D2R complexes due to the possibility that MOR upon morphine treatment can develop a higher affinity for DOR. As a result, increased numbers of D2R monomers/homomers in these neurons become free to interact with the A2A receptors found in high densities within such neurons. Increased numbers of A2AR-D2R heteroreceptor complexes are formed and contribute to enhanced firing of these antireward neurons due to loss of inhibitory D2R protomer signaling which finally leads to the development of morphine use disorder. Development of cocaine use disorder may instead be reduced through enkephalin induced activation of the MOR-DOR complex inhibiting the activity of the enkephalin positive GABA antireward neurons. Altogether, we propose that these altered complexes could be pharmacological targets to modulate the reward and the development of substance use disorders.
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spelling pubmed-80055302021-03-30 The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders Borroto-Escuela, Dasiel O. Wydra, Karolina Fores-Pons, Ramon Vasudevan, Lakshmi Romero-Fernandez, Wilber Frankowska, Małgorzata Ferraro, Luca Beggiato, Sarah Crespo-Ramirez, Minerva Rivera, Alicia Rocha, Luisa L. Perez de la Mora, Miguel Stove, Christophe Filip, Małgorzata Fuxe, Kjell Front Pharmacol Pharmacology The widespread distribution of heteroreceptor complexes with allosteric receptor-receptor interactions in the CNS represents a novel integrative molecular mechanism in the plasma membrane of neurons and glial cells. It was proposed that they form the molecular basis for learning and short-and long-term memories. This is also true for drug memories formed during the development of substance use disorders like morphine and cocaine use disorders. In cocaine use disorder it was found that irreversible A2AR-D2R complexes with an allosteric brake on D2R recognition and signaling are formed in increased densities in the ventral enkephalin positive striatal-pallidal GABA antireward neurons. In this perspective article we discuss and propose how an increase in opioid heteroreceptor complexes, containing MOR-DOR, MOR-MOR and MOR-D2R, and their balance with each other and A2AR-D2R complexes in the striatal-pallidal enkephalin positive GABA antireward neurons, may represent markers for development of morphine use disorders. We suggest that increased formation of MOR-DOR complexes takes place in the striatal-pallidal enkephalin positive GABA antireward neurons after chronic morphine treatment in part through recruitment of MOR from the MOR-D2R complexes due to the possibility that MOR upon morphine treatment can develop a higher affinity for DOR. As a result, increased numbers of D2R monomers/homomers in these neurons become free to interact with the A2A receptors found in high densities within such neurons. Increased numbers of A2AR-D2R heteroreceptor complexes are formed and contribute to enhanced firing of these antireward neurons due to loss of inhibitory D2R protomer signaling which finally leads to the development of morphine use disorder. Development of cocaine use disorder may instead be reduced through enkephalin induced activation of the MOR-DOR complex inhibiting the activity of the enkephalin positive GABA antireward neurons. Altogether, we propose that these altered complexes could be pharmacological targets to modulate the reward and the development of substance use disorders. Frontiers Media S.A. 2021-03-15 /pmc/articles/PMC8005530/ /pubmed/33790790 http://dx.doi.org/10.3389/fphar.2021.627032 Text en Copyright © 2021 Borroto-Escuela, Wydra, Fores-Pons, Vasudevan, Romero-Fernandez, Frankowska, Ferraro, Beggiato, Crespo-Ramirez, Rivera, Rocha, Perez de la Mora, Stove, Filip and Fuxe. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Borroto-Escuela, Dasiel O.
Wydra, Karolina
Fores-Pons, Ramon
Vasudevan, Lakshmi
Romero-Fernandez, Wilber
Frankowska, Małgorzata
Ferraro, Luca
Beggiato, Sarah
Crespo-Ramirez, Minerva
Rivera, Alicia
Rocha, Luisa L.
Perez de la Mora, Miguel
Stove, Christophe
Filip, Małgorzata
Fuxe, Kjell
The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
title The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
title_full The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
title_fullStr The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
title_full_unstemmed The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
title_short The Balance of MU-Opioid, Dopamine D2 and Adenosine A2A Heteroreceptor Complexes in the Ventral Striatal-Pallidal GABA Antireward Neurons May Have a Significant Role in Morphine and Cocaine Use Disorders
title_sort balance of mu-opioid, dopamine d2 and adenosine a2a heteroreceptor complexes in the ventral striatal-pallidal gaba antireward neurons may have a significant role in morphine and cocaine use disorders
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005530/
https://www.ncbi.nlm.nih.gov/pubmed/33790790
http://dx.doi.org/10.3389/fphar.2021.627032
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