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Upon cocaine self-administration, this antagonistic A2AR\u2013D2R interaction disappeared in the dorsal striatum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In the current experiments, it was tested whether such modifications in the antagonistic A2AR\u2013D2R receptor\u2013receptor interactions can develop also after an acute systemic injection of a low cocaine dose (1\u00a0mg\/kg; sc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Microdialysis experiments indicated that acute cocaine did not significantly alter the extracellular dopamine levels in the dorsal striatum of the awake Wistar rats. Competition dopamine receptor binding experiments demonstrated that in the acute cocaine group, the A2AR agonist CGS-21680 produced significantly larger increases in the D2R<jats:italic>K<\/jats:italic><jats:sub>i, High<\/jats:sub>values (reduction of high-affinity) versus the saline-injected (i.e. control) group. Furthermore, in the dorsal striatum membrane preparation from acute cocaine-injected rats, CGS-21680 also produced significant increases in the D2R<jats:italic>K<\/jats:italic><jats:sub>i, Low<\/jats:sub>values (reduction of low-affinity) and in the proportion of D2Rs in the high-affinity state (RH). Such significant effects were not observed with CGS-21680 in the control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The molecular mechanism involved in the acute cocaine-induced increase in the antagonistic allosteric A2AR\u2013D2R receptor\u2013receptor interactions may be an increased formation of higher-order complexes A2AR\u2013D2R-sigma1R in which cocaine by binding to the sigma1R protomer also allosterically enhances the inhibitory A2AR\u2013D2R interaction in this receptor complex.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s43440-020-00069-3","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T12:02:32Z","timestamp":1583150552000},"page":"332-339","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Acute cocaine treatment enhances the antagonistic allosteric adenosine A2A-dopamine D2 receptor\u2013receptor interactions in rat dorsal striatum without increasing significantly extracellular dopamine levels"],"prefix":"10.1007","volume":"72","author":[{"given":"Wilber","family":"Romero-Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zilong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Beggiato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Wydra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Filip","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Tanganelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dasiel O.","family":"Borroto-Escuela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Ferraro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kjell","family":"Fuxe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"issue":"16","key":"69_CR1","doi-asserted-by":"publisher","first-page":"7238","DOI":"10.1073\/pnas.88.16.7238","volume":"88","author":"S Ferre","year":"1991","unstructured":"Ferre S, von Euler G, Johansson B, Fredholm BB, Fuxe K. 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