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In order to study the pharmacokinetics of heroin and its active metabolites after i.v. administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (<jats:styled-content style=\"fixed-case\">ECF<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>After an i.v. bolus injection of heroin to freely moving <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>prague\u2013<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>awley rats, the concentrations of heroin and metabolites in blood samples from the vena jugularis and in microdialysis samples from striatal brain <jats:styled-content style=\"fixed-case\">ECF<\/jats:styled-content> were measured by ultraperformance LC\u2010MS\/MS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Heroin levels decreased very fast, both in blood and brain <jats:styled-content style=\"fixed-case\">ECF<\/jats:styled-content>, and could not be detected after 18 and 10\u2009min respectively. 6\u2010Monoacetylmorphine (6\u2010<jats:styled-content style=\"fixed-case\">MAM<\/jats:styled-content>) increased very rapidly, reaching its maximal concentrations after 2.0 and 4.3\u2009min, respectively, and falling thereafter. Morphine increased very slowly, reaching its maximal levels, which were six times lower than the highest 6\u2010<jats:styled-content style=\"fixed-case\">MAM<\/jats:styled-content> concentrations, after 12.6 and 21.3\u2009min, with a very slow decline during the rest of the experiment and only surpassing 6\u2010<jats:styled-content style=\"fixed-case\">MAM<\/jats:styled-content> levels at least 30\u2009min after injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>After an i.v. heroin injection, 6\u2010<jats:styled-content style=\"fixed-case\">MAM<\/jats:styled-content> was the predominant opioid present shortly after injection and during the first 30\u2009min, not only in the blood but also in rat brain <jats:styled-content style=\"fixed-case\">ECF<\/jats:styled-content>. 6\u2010<jats:styled-content style=\"fixed-case\">MAM<\/jats:styled-content> might therefore mediate most of the effects observed shortly after heroin intake, and this finding questions the general assumption that morphine is the main and most important metabolite of heroin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12305","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T14:31:44Z","timestamp":1376490704000},"page":"546-556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats"],"prefix":"10.1111","volume":"170","author":[{"given":"A","family":"Gott\u00e5s","sequence":"first","affiliation":[{"name":"Department of Drug Abuse Research and Method Development Division of Forensic Medicine and Drug Abuse Research Norwegian Institute of Public Health  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E L","family":"\u00d8iestad","sequence":"additional","affiliation":[{"name":"Department of 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