{"entity": "publication", "iuid": "0fe670c9f1ad4a88b441a5a41c81ab07", "timestamp": "2026-08-26T22:47:59.560Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0fe670c9f1ad4a88b441a5a41c81ab07.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0fe670c9f1ad4a88b441a5a41c81ab07"}}, "title": "OSU-6162, a Sigma1R Ligand in Low Doses, Can Further Increase the Effects of Cocaine Self-Administration on Accumbal D2R Heteroreceptor Complexes.", "authors": [{"family": "Borroto-Escuela", "given": "Dasiel O", "initials": "DO", "orcid": "0000-0002-5736-373X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc1e0b27e62849af8026971185dc29b9.json"}}, {"family": "Romero-Fernandez", "given": "Wilber", "initials": "W"}, {"family": "Wydra", "given": "Karolina", "initials": "K"}, {"family": "Zhou", "given": "Zilong", "initials": "Z"}, {"family": "Suder", "given": "Agata", "initials": "A"}, {"family": "Filip", "given": "Malgorzata", "initials": "M"}, {"family": "Fuxe", "given": "Kjell", "initials": "K"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Neurotox Res", "issn": "1476-3524", "volume": "37", "issue": "2", "pages": "433-444", "issn-l": null}, "abstract": "Cocaine was previously shown to act at the Sigma1R which is a target for counteracting cocaine actions. It therefore becomes of interest to test if the monoamine stabilizer (-) OSU-6162 (OSU-6162) with a nanomolar affinity for the Sigma1R can acutely modulate in low doses the effects of cocaine self-administration. In behavioral studies, OSU-6162 (5 mg/kg, s.c.) did not significantly change the number of active lever pressing and cocaine infusions. However, a trend to reduce cocaine readouts was found after 3 days of treatment. In contrast, in maintenance of cocaine self-administration, the proximity ligation assay performed on brains from rats pretreated with OSU-6162 showed highly significant increases in the density of the D2R-Sigma1R heteroreceptor complexes in the shell of the nucleus accumbens versus OSU-6162 induced increases in this region of yoked saline rats. In cocaine self-administration, highly significant increases were also induced by OSU-6162 in the A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell versus vehicle-treated rats. Furthermore, ex vivo, the A2AR agonist CGS21680 (100 nM) produced a marked and significant increase of the D2R Ki high values in the OSU-6162-treated versus vehicle-treated rats under maintenance of cocaine self-administration. These results indicate a substantial increase in the inhibitory allosteric A2AR-D2R interactions following cocaine self-administration upon activation by the A2AR agonist ex vivo. The current results indicate that OSU-6162 via its high affinity for the Sigma1R may increase the number of accumbal shell D2R-Sigma1R and A2AR-D2R heteroreceptor complexes associated with further increases in the antagonistic A2AR-D2R interactions in cocaine self-administration.", "doi": "10.1007/s12640-019-00134-7", "pmid": "31782100", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6989596"}, {"db": "pii", "key": "10.1007/s12640-019-00134-7"}], "notes": [], "created": "2026-08-21T11:09:05.241Z", "modified": "2026-08-21T11:09:05.303Z"}