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Brain mechanisms for the establishment of addiction\u2010related behaviors are still not fully understood, and specific biomarkers for cocaine use are not available. Sphingolipids are major membrane lipids, which shape neuronal membrane composition and dynamics in the brain. Here, we investigated how chronic cocaine exposure during establishment of addiction\u2010related behaviors affects the activity of the sphingolipid rheostat controlling enzymes in the brain of rats. As we detected specific effects on several enzymes in the brain, we tested whether the activity of selected enzymes in the blood may serve as potential biomarker for cocaine exposure in non\u2010human primates (<jats:styled-content style=\"fixed-case\"><jats:italic>Callithrix penicillata<\/jats:italic><\/jats:styled-content>). We found that intravenous cocaine self\u2010administration led to a reduced mRNA expression of <jats:italic>Cers1<\/jats:italic>, <jats:italic>Degs1<\/jats:italic> and <jats:italic>Degs2<\/jats:italic>, and <jats:italic>Smpd1<\/jats:italic> in the prefrontal cortex of rats, as well as a reduction of <jats:italic>Cers4<\/jats:italic> expression in the striatum. These effects reversed after 10 days of abstinence. Monkeys showed a robust cocaine\u2010induced place preference (CPP). This coincided with a reduction in blood acid sphingomyelinase (ASM) activity after CPP establishment. This effect normalized after 15 days of abstinence. Altogether, these findings suggest that the establishment of cocaine addiction\u2010related behaviors coincides with changes in the activity of sphingolipid controlling enzymes. In particular, blood ASM levels may serve as a translational biomarker for recent cocaine exposure.<\/jats:p>","DOI":"10.1111\/adb.12955","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T03:51:42Z","timestamp":1596685902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cocaine attenuates acid sphingomyelinase activity during establishment of addiction\u2010related behavior\u2014A translational study in rats and monkeys"],"prefix":"10.1111","volume":"26","author":[{"given":"Ma\u0142gorzata","family":"Frankowska","sequence":"first","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Polish Academy of Sciences Maj Institute of Pharmacology  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando M.","family":"Jesus","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences University of Brasilia  Brasilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"M\u00fchle","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica V.N.","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences University of Brasilia  Brasilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael S.","family":"Maior","sequence":"additional","affiliation":[{"name":"Department of Physiological Sciences University of Bras\u00edlia  Brasilia Brazil"},{"name":"Primate Center Institute of Biology, University of Brasilia  Brasilia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sadakierska\u2010Chudy","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Polish Academy of Sciences Maj Institute of Pharmacology  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Smaga","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Polish Academy of Sciences Maj Institute of Pharmacology  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Piechota","sequence":"additional","affiliation":[{"name":"Department of Molecular Neuropharmacology, Polish Academy of Sciences Maj Institute of Pharmacology  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liubov S.","family":"Kalinichenko","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology University of Duisburg\u2010Essen  Essen Germany"},{"name":"Department of Surgery University of Cincinnati  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Kornhuber","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Filip","sequence":"additional","affiliation":[{"name":"Department of Drug Addiction Pharmacology, Polish Academy of Sciences Maj Institute of Pharmacology  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5325-9900","authenticated-orcid":false,"given":"Christian P.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy Friedrich\u2010Alexander\u2010University Erlangen\u2010N\u00fcrnberg (FAU)  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilia","family":"Barros","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Health Sciences University of Brasilia  Brasilia Brazil"},{"name":"Primate Center Institute of Biology, University of Brasilia  Brasilia 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