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oai:repisalud.isciii.es:20.500.12105/182872024-11-28T15:14:33Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Borroto-Escuela, Dasiel O. author Wydra, Karolina author Fores-Pons, Ramon author Vasudevan, Lakshmi author Romero-Fernandez, Wilber author Frankowska, Małgorzata author Ferraro, Luca author Beggiato, Sarah author Crespo-Ramirez, Minerva author Rivera, Alicia author Rocha, Luisa L. author Perez de la Mora, Miguel author Stove, Christophe author Filip, Małgorzata author Fuxe, Kjell authoraffiliation [Borroto-Escuela,DO; Fores-Pons,R; Romero-Fernandez,W; Fuxe,K] Department of Neuroscience, Karolinska Institutet, Biomedicum, Stockholm, Sweden. [Wydra,K; Frankowska,M; Filip,M] Department of Drug Addiction Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. [Vasudevan,L; Stove,CC] Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. [Ferraro,L] Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy. [Beggiato,S] Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Chieti, Italy. [Crespo-Ramirez,M; Perez de la Mora,M] Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico. [Rivera,A] Department of Cell Biology, University of Malaga, Instituto de Investigación Biomédica (IBIMA), Malaga, Spain. [Rocha,LL] Pharmacobiology Department, Center for Research and Advanced Studies, Mexico City, Mexico 2024-02-19T15:26:30Z 2024-02-19T15:26:30Z 2021-03-15 10.3389/fphar.2021.627032 1663-9812 Frontiers in Pharmacology http://hdl.handle.net/10668/4551 33790790 http://hdl.handle.net/20.500.12105/18287 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. eng G protein-coupled receptor Mu opioid receptor Dopamine D2 receptor Adenosine A2A receptor Morphine use disorder Cocaine use disorder Oligomerization Morphine Neurons Enkephalins Receptores acoplados a proteínas G Receptores opioides mu Receptores de dopamina D2 Receptor de adenosina A2A Morfina Trastornos relacionados con sustancias Cocaína Neuronas Encefalinas 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 research article