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Pharmacokinetic insights into behavioral differences in heroin and cocaine self-administration and choice procedures
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  • Ginevra D'Ottavio,
  • Sara Pezza,
  • Jacopo Modoni,
  • Ingrid Reverte,
  • Claudia Marchetti,
  • Soami Zenoni,
  • Silvana De Pirro,
  • Daniela Maftei,
  • Roberta Lattanzi,
  • Giuseppe Esposito,
  • Davide Ragozzino,
  • Emiliano Merlo,
  • Marco Venniro,
  • Roberto Ciccocioppo,
  • Fabio Fumagalli,
  • Michele Milella,
  • Aldo Badiani,
  • Fernando Boix Escolán,
  • Daniele Caprioli
Ginevra D'Ottavio
University of Rome La Sapienza
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Sara Pezza
University of Rome La Sapienza
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Jacopo Modoni
Santa Lucia Foundation Institute for Hospitalization and Care Scientific
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Ingrid Reverte
Link Campus University
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Claudia Marchetti
University of Rome La Sapienza
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Soami Zenoni
Santa Lucia Foundation Institute for Hospitalization and Care Scientific
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Silvana De Pirro
Haukeland University Hospital
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Daniela Maftei
University of Rome La Sapienza
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Roberta Lattanzi
University of Rome La Sapienza
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Giuseppe Esposito
University of Rome La Sapienza
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Davide Ragozzino
University of Rome La Sapienza
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Emiliano Merlo
University of Sussex
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Marco Venniro
University of Maryland School of Medicine
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Roberto Ciccocioppo
University of Camerino
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Fabio Fumagalli
University of Milan
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Michele Milella
Umberto I Polyclinic of Rome
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Aldo Badiani
University of Rome La Sapienza
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Fernando Boix Escolán
Oslo University Hospital
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Daniele Caprioli
University of Rome La Sapienza

Corresponding Author:[email protected]

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Abstract

Background and Purpose. Heroin and cocaine users tailor their dosage, frequency, and method of administration, to maximize the drugs’ effects or prevent withdrawal symptoms. Counterintuitively, preclinical self-administration and choice experiments employ fixed unit-doses and timeouts (after doses) largely resulting in uniform drug-taking patterns. The application of these procedures also disregards the distinct pharmacokinetic properties of heroin and cocaine. This uniformity contrasts with the significantly different ways humans tailor their dosage and frequency of heroin and cocaine use. Here, by combining behavioral and pharmacokinetics assessments we revealed that self-administration procedures lacking the timeout may overcomes this limitation. Experimental Approach. We analyzed heroin and cocaine taking- and seeking-patterns and estimated drug-brain levels in the presence or absence of timeout. We further assessed how absence of timeout and the availability of drug or social peer (access time to the two rewards) affect drug preference in choice procedures. Key Results. Removing the timeout had a profound effect on heroin-taking patterns and seeking, promoting the emergence of burst-like intake, yielding higher brain peak concentrations of heroin. Timeout removal had marginal impact on cocaine taking patterns and seeking. Increasing the access time to the drug in the discrete choice procedure resulted in higher drug intake and increased preference for heroin, but it did not alter cocaine preference. Conclusion and Implications. Removing timeout during self-administration revealed distinct heroin and cocaine taking patterns. Self-administration without timeout and access to high heroin doses during choice more closely mimic human heroin taking patterns and related behaviors, including maladaptive choices.
27 Oct 2024Submitted to British Journal of Pharmacology
29 Oct 2024Submission Checks Completed
29 Oct 2024Assigned to Editor
29 Oct 2024Review(s) Completed, Editorial Evaluation Pending
02 Nov 2024Reviewer(s) Assigned