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A2AR Transmembrane 2 Peptide Administration Disrupts the A2AR-A2AR Homoreceptor but Not the A2AR-D2R Heteroreceptor Complex: Lack of Actions on Rodent Cocaine Self-Administration
Karolinska Inst, Dept Neurosci, S-16175 Stockholm, Sweden;Univ Urbino, Physiol Sect, Dept Biomol Sci, Campus Sci Enrico Mattei,Via Cale Suore 2, I-61029 Urbino, Italy;Observ Cubano Neurociencias, Grp Bohio Estudio, Zayas 50, Yaguajay 62100, Cuba.
Polish Acad Sci, Dept Drug Addict Pharmacol, Maj Inst Pharmacol, PL-31343 Krakow, Poland.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology. Karolinska Inst, Dept Neurosci, S-16175 Stockholm, Sweden.
Karolinska Inst, Dept Neurosci, S-16175 Stockholm, Sweden;Northeast Normal Univ, Natl Engn Lab Druggable Gene & Prot Screening, Changchun 130024, Jilin, Peoples R China.
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 23, article id 6100Article in journal (Refereed) Published
Abstract [en]

It was previously demonstrated that rat adenosine A2AR transmembrane V peptide administration into the nucleus accumbens enhances cocaine self-administration through disruption of the A2AR-dopamine (D2R) heteroreceptor complex of this region. Unlike human A2AR transmembrane 4 (TM4) and 5 (TM5), A2AR TM2 did not interfere with the formation of the A2AR-D2R heteroreceptor complex in cellular models using BRET1 assay. A2AR TM2 was proposed to be part of the of the receptor interface of the A2AR homomer instead and was therefore tested in the current article for effects on rat cocaine self-administration using rat A2AR synthetic TM2 peptide bilaterally injected into the nucleus accumbens. The injected A2AR TM2 peptide failed to significantly counteract the inhibitory action of the A2AR agonist CGS 21680 (0.1 mg/Kg) on cocaine self-administration. In line with these results, the microinjected A2AR TM2 peptide did not reduce the number of proximity ligation assay blobs identifying A2AR-D2R heteroreceptor complexes in the nucleus accumbens. In contrast, the A2AR TM2 peptide significantly reduced the number of A2AR-A2AR homoreceptor complexes in the nucleus accumbens. As to effects on the receptor-receptor interactions in the A2AR-D2R heteroreceptor complexes, the A2AR TM2 peptide did not alter the significant increase in the D2R Ki, high values produced by the A2AR agonist CGS 21680 ex vivo in the ventral striatum. The results indicate that the accumbal A2AR-A2AR homomeric complexes are not involved in mediating the A2AR agonist-induced inhibition of cocaine self-administration.

Place, publisher, year, edition, pages
MDPI , 2019. Vol. 20, no 23, article id 6100
Keywords [en]
adenosine A2A receptor, dopamine D2 receptor, homoreceptor complexes, heteroreceptor complexes, allosteric receptor-receptor interactions, cocaine use disorder, small interfering peptides: G protein-coupled receptors
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-402657DOI: 10.3390/ijms20236100ISI: 000504428300282PubMedID: 31816953OAI: oai:DiVA.org:uu-402657DiVA, id: diva2:1387011
Funder
Swedish Research Council, 62X-00715-50-3The Swedish Brain Foundation, F02018-0286The Swedish Brain Foundation, F02019-0296Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-20Bibliographically approved

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Romero Fernandez, WilberFrankowska, Malgorzata
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