Ranking the contribution of behavioral measures comprising oxycodone self-administration to reinstatement of drug-seeking in male and female rats

Suman K. Guha, Yanaira Alonso-Caraballo, Gillian S. Driscoll, Jessica A. Babb, Megan Neal, Nicholas J. Constantino, Tania Lintz, Elizabeth Kinard, Elena H. Chartoff

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3 Scopus citations

Abstract

Introduction: Rates of relapse to drug use during abstinence are among the highest for opioid use disorder (OUD). In preclinical studies, reinstatement to drug-seeking has been extensively studied as a model of relapse–but the work has been primarily in males. We asked whether biological sex contributes to behaviors comprising self-administration of the prescription opioid oxycodone in rats, and we calculated the relative contribution of these behavioral measures to reinstatement in male and female rats. Materials and methods: Rats were trained to self-administer oxycodone (8 days, training phase), after which we examined oxycodone self-administration behaviors for an additional 14 days under three conditions in male and female rats: short access (ShA, 1 h/d), long access (LgA, 6 h/d), and saline self-administration. All rats were then tested for cue-induced reinstatement of drug-seeking after a 14-d forced abstinence period. We quantified the # of infusions, front-loading of drug intake, non-reinforced lever pressing, inter-infusion intervals, escalation of intake, and reinstatement responding on the active lever. Results: Both male and female rats in LgA and ShA conditions escalated oxycodone intake to a similar extent. However, males had higher levels of non-reinforced responding than females under LgA conditions, and females had greater levels of reinstatement responding than males. We then correlated each addiction-related measure listed above with reinstatement responding in males and females and ranked their respective relative contributions. Although the majority of behavioral measures associated with oxycodone self-administration did not show sex differences on their own, when analyzed together using partial least squares regression, their relative contributions to reinstatement were sex-dependent. Front-loading behavior was calculated to have the highest relative contribution to reinstatement in both sexes, with long and short inter-infusion intervals having the second greatest contribution in females and males, respectively. Discussion: Our results demonstrate sex differences in some oxycodone self-administration measures. More importantly, we demonstrate that a sex- dependent constellation of self-administration behaviors can predict the magnitude of reinstatement, which holds great promise for relapse prevention in people.

Original languageEnglish (US)
Article number1035350
JournalFrontiers in Behavioral Neuroscience
Volume16
DOIs
StatePublished - Nov 24 2022

Bibliographical note

Funding Information:
This work was supported by grants from the National Institute on Drug Abuse (DA045000) to EC and KOODA053527 to YA-C.

Publisher Copyright:
Copyright © 2022 Guha, Alonso-Caraballo, Driscoll, Babb, Neal, Constantino, Lintz, Kinard and Chartoff.

Keywords

  • escalation
  • female
  • front-loading
  • opioid
  • relapse
  • sex difference
  • vulnerability

PubMed: MeSH publication types

  • Journal Article

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