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Modifications of diet composition may lead to metabolic and mental disorders that may predispose offspring to a substance use disorder. We assessed the impact of a maternal high\u2010sugar diet (HSD, rich in sucrose) consumed during pregnancy and lactation on the offspring phenotype in the context of the rewarding and motivational effects of cocaine and changes within the central melanocortin (MC) system. Using an intravenous cocaine self\u2010administration model, we showed that maternal HSD leads to increased relapse of cocaine\u2010seeking behavior in male offspring. In addition, we demonstrated that cocaine induces changes in the level of MC\u20104 receptors in the offspring brain, and these changes depend on maternal diet. These studies also reveal that an MC\u20104 receptor antagonist reduces the reinstatement of cocaine\u2010seeking behavior, and offspring exposed to maternal HSD are more sensitive to its effects than offspring exposed to the maternal control diet. Taken together, the results suggest that a maternal HSD and MC\u20104 receptors play an important role in cocaine relapse.<\/jats:p>","DOI":"10.1096\/fj.202000163r","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T08:43:47Z","timestamp":1589791427000},"page":"9192-9206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Maternal high\u2010sugar diet changes offspring vulnerability to reinstatement of cocaine\u2010seeking behavior: Role of melanocortin\u20104 receptors"],"prefix":"10.1096","volume":"34","author":[{"given":"Dawid","family":"Gawli\u0144ski","sequence":"first","affiliation":[{"name":"Department of Drug Addiction Pharmacology Maj Institute of Pharmacology Polish Academy of Sciences Krak\u00f3w Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinga","family":"Gawli\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Drug 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