RT Journal Article
T1 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
A1 Borroto-Escuela, Dasiel O.
A1 Wydra, Karolina
A1 Fores-Pons, Ramon
A1 Vasudevan, Lakshmi
A1 Romero-Fernandez, Wilber
A1 Frankowska, Małgorzata
A1 Ferraro, Luca
A1 Beggiato, Sarah
A1 Crespo-Ramirez, Minerva
A1 Rivera, Alicia
A1 Rocha, Luisa L.
A1 Perez de la Mora, Miguel
A1 Stove, Christophe
A1 Filip, Małgorzata
A1 Fuxe, Kjell
K1 G protein-coupled receptor
K1 Mu opioid receptor
K1 Dopamine D2 receptor
K1 Adenosine A2A receptor
K1 Morphine use disorder
K1 Cocaine use disorder
K1 Oligomerization
K1 Morphine
K1 Neurons
K1 Enkephalins
K1 Receptores acoplados a proteínas G
K1 Receptores opioides mu
K1 Receptores de dopamina D2
K1 Receptor de adenosina A2A
K1 Morfina
K1 Trastornos relacionados con sustancias
K1 Cocaína
K1 Neuronas
K1 Encefalinas
AB 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.
PB Frontiers
YR 2021
FD 2021-03-15
LK http://hdl.handle.net/10668/4551
UL http://hdl.handle.net/10668/4551
LA en
NO Borroto-Escuela DO, Wydra K, Fores-Pons R, Vasudevan L, Romero-Fernandez W, Frankowska M, et al. 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. Front Pharmacol. 2021 Mar 15;12:627032
DS RISalud
RD Jun 1, 2025