{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:44:16Z","timestamp":1789919056311,"version":"4.0.1"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T00:00:00Z","timestamp":1553126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education, Warszawa, Poland","award":["N N404 273040"],"award-info":[{"award-number":["N N404 273040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>There is strong support for the role of the endocannabinoid system and the noncannabinoid lipid signaling molecules, N-acylethanolamines (NAEs), in cocaine reward and withdrawal. In the latest study, we investigated the changes in the levels of the above molecules and expression of cannabinoid receptors (CB1 and CB2) in several brain regions during cocaine-induced reinstatement in rats. By using intravenous cocaine self-administration and extinction procedures linked with yoked triad controls, we found that a priming dose of cocaine (10 mg\/kg, i.p.) evoked an increase of the anadamide (AEA) level in the hippocampus and prefrontal cortex only in animals that had previously self-administered cocaine. In the same animals, the level of 2-arachidonoylglycerol (2-AG) increased in the hippocampus and nucleus accumbens. Moreover, the drug-induced relapse resulted in a potent increase in NAEs levels in the cortical areas and striatum and, at the same time, a decrease in the tissue levels of oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) was noted in the nucleus accumbens, cerebellum, and\/or hippocampus. At the level of cannabinoid receptors, a priming dose of cocaine evoked either upregulation of the CB1 and CB2 receptors in the prefrontal cortex and lateral septal nuclei or downregulation of the CB1 receptors in the ventral tegmental area. In the medial globus pallidus we observed the upregulation of the CB2 receptor only after yoked chronic cocaine treatment. Our findings support that in the rat brain, the endocannabinoid system and NAEs are involved in cocaine induced-reinstatement where these molecules changed in a region-specific manner and may represent brain molecular signatures for the development of new treatments for cocaine addiction.<\/jats:p>","DOI":"10.3390\/molecules24061125","type":"journal-article","created":{"date-parts":[[2019,3,21]],"date-time":"2019-03-21T12:28:01Z","timestamp":1553171281000},"page":"1125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Cocaine-Induced Reinstatement of Cocaine Seeking Provokes Changes in the Endocannabinoid and N-Acylethanolamine Levels in Rat Brain Structures"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6501-8656","authenticated-orcid":false,"given":"Beata","family":"Bystrowska","sequence":"first","affiliation":[{"name":"Department of Toxicology, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Frankowska","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, PL 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Smaga","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, PL 31-343 Krak\u00f3w, Poland"},{"name":"Department of Internal Medicine, Jagiellonian University Medical College, Skawi\u0144ska 8, PL 31-066 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7310-1556","authenticated-orcid":false,"given":"Ewa","family":"Niedzielska-Andres","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucyna","family":"Pomierny-Chamio\u0142o","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Collegium Medicum, Jagiellonian University, Medyczna 9, PL 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4321-7942","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Sm\u0119tna 12, PL 31-343 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,21]]},"reference":[{"key":"ref_1","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (2018). 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