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Counterintuitively, preclinical self\u2010administration and choice experiments employ, almost invariably and regardless of the pharmacokinetic properties of the drug under examination, fixed unit\u2010doses and timeouts (after unit\u2010doses) largely resulting in uniform drug\u2010taking patterns. This uniformity contrasts with the large variability observed in humans, which serves as critical indicator of addiction severity and treatment success. Here, by combining behavioural and pharmacokinetics assessments, we revealed that drug self\u2010administration procedures without timeouts may overcome this limitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We analysed heroin\u2010 and cocaine\u2010taking patterns and seeking and estimated drug\u2010brain levels in the presence or absence of timeout under different training conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Removing timeouts had a profound effect on heroin\u2010taking patterns and seeking, promoting the emergence of burst\u2010like intake, yielding higher brain peak concentrations of heroin. In contrast, the removal of timeout had marginal impact on cocaine\u2010taking patterns and seeking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The removal of timeout during self\u2010administration revealed distinct cocaine and heroin patterns, with the latter closely resembling human heroin use patterns.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70023","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T08:25:02Z","timestamp":1743323102000},"page":"2968-2985","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Behavioural and pharmacokinetic analysis of heroin and cocaine self\u2010administration: Effects of timeout on self\u2010administration and choice in male rats"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0475-6641","authenticated-orcid":false,"given":"Ginevra","family":"D'Ottavio","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. 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