1. Understanding the Functional Plasticity in Neural Networks of the Basal Ganglia in Cocaine Use Disorder: A Role for Allosteric Receptor-Receptor Interactions in A2A-D2 Heteroreceptor Complexes
- Author
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Borroto-Escuela, Dasiel O., Wydra, Karolina, Pintsuk, Julia, Narvaez, Manuel, Corrales, Fidel, Zaniewska, Magdalena, Agnati, Luigi F., Franco, Rafael, Tanganelli, Sergio, Ferraro, Luca, Filip, Malgorzata, Fuxe, Kjell, [Borroto-Escuela, Dasiel O.] Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden, [Pintsuk, Julia] Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden, [Agnati, Luigi F.] Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden, [Fuxe, Kjell] Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden, [Borroto-Escuela, Dasiel O.] Univ Urbino, Physiol Sect, Dept Biomol Sci, Campus Sci Enrico Mattei,Via Cale Suore 2, I-61029 Urbino, Italy, [Borroto-Escuela, Dasiel O.] Observ Cubanos Neurociencias, Grp Bohio Estudio, Yaguajay, Cuba, [Corrales, Fidel] Observ Cubanos Neurociencias, Grp Bohio Estudio, Yaguajay, Cuba, [Wydra, Karolina] Polish Acad Sci, Inst Pharmacol, Lab Drug Addict Pharmacol, 12 Smetna St, PL-31343 Krakow, Poland, [Zaniewska, Magdalena] Polish Acad Sci, Inst Pharmacol, Lab Drug Addict Pharmacol, 12 Smetna St, PL-31343 Krakow, Poland, [Filip, Malgorzata] Polish Acad Sci, Inst Pharmacol, Lab Drug Addict Pharmacol, 12 Smetna St, PL-31343 Krakow, Poland, [Pintsuk, Julia] Univ Tartu, Inst Biomed & Translat Med, Dept Physiol, 19 Ravila St, EE-50411 Tartu, Estonia, [Narvaez, Manuel] Univ Malaga, Inst Invest Biomed Malaga, Fac Med, Malaga, Spain, [Corrales, Fidel] Univ Malaga, Inst Invest Biomed Malaga, Fac Med, Malaga, Spain, [Corrales, Fidel] Ctr Nacl Neurociencias, Havana, Cuba, [Franco, Rafael] Univ Barcelona, Fac Biol, Dept Bioquim & Biomed Mol, Barcelona, Spain, [Franco, Rafael] Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Madrid, Spain, [Tanganelli, Sergio] Univ Ferrara, Dept Life Sci & Biotechnol, Ferrara, Italy, [Ferraro, Luca] Univ Ferrara, Dept Life Sci & Biotechnol, Ferrara, Italy, [Tanganelli, Sergio] Univ Ferrara, Dept Med Sci, Ferrara, Italy, Swedish Medical Research Council, AFA Forsakring, Hjarnfonden, and Institute of Pharmacology Polish Academy of Sciences (Krakow, Poland)
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D2 receptors ,Modulation ,Article Subject ,Synaptic-transmission ,Adenosine a(2a) receptors ,Dopamine ,Communication ,Integrative mechanism ,Glutamate ,Proximity ligation assay ,Higher-order oligomers - Abstract
Our hypothesis is that allosteric receptor-receptor interactions in homo- and heteroreceptor complexes may form the molecular basis of learning and memory. This principle is illustrated by showing how cocaine abuse can alter the adenosine A2AR-dopamine D2R heterocomplexes and their receptor-receptor interactions and hereby induce neural plasticity in the basal ganglia. Studies with A2AR ligands using cocaine self-administration procedures indicate that antagonistic allosteric A2AR-D2R heterocomplexes of the ventral striatopallidal GABA antireward pathway play a significant role in reducing cocaine induced reward, motivation, and cocaine seeking. Anticocaine actions of A2AR agonists can also be produced at A2AR homocomplexes in these antireward neurons, actions in which are independent of D2R signaling. At the A2AR-D2R heterocomplex, they are dependent on the strength of the antagonistic allosteric A2AR-D2R interaction and the number of A2AR-D2R and A2AR-D2R-sigma1R heterocomplexes present in the ventral striatopallidal GABA neurons. It involves a differential cocaine-induced increase in sigma1Rs in the ventral versus the dorsal striatum. In contrast, the allosteric brake on the D2R protomer signaling in the A2AR-D2R heterocomplex of the dorsal striatopallidal GABA neurons is lost upon cocaine self-administration. This is potentially due to differences in composition and allosteric plasticity of these complexes versus those in the ventral striatopallidal neurons.
- Published
- 2016