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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8005530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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