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Impact of Sex on Heroin Intravenous Self-Administration by Heterogeneous Stock Rats
Michael A Taffe1, Sydney L Mehl1, Sara R M U Rahman1
1Department of Psychiatry, University of California, San Diego; La Jolla, CA, USA.
Biorxiv : the Preprint Server for Biology
|April 17, 2026
Summary
Female Heterogeneous Stock (HS) rats self-administered more opioids than males, indicating sex differences in opioid intake. This study highlights the importance of sex as a biological variable in addiction research.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Genetics
Background:
- Opioid intravenous self-administration (IVSA) studies in rats often show no sex differences or higher intake in females.
- Methodological variations complicate consistent findings on sex differences in opioid IVSA.
Purpose of the Study:
- To investigate sex differences in opioid IVSA using genetically diverse Heterogeneous Stock (HS) rats.
- To determine if HS rats exhibit sex-specific patterns in the self-administration of heroin, oxycodone, and fentanyl.
Main Methods:
- Male and female HS rats underwent heroin IVSA training under a Fixed Ratio 1 (FR-1) schedule.
- Dose-response curves for heroin, oxycodone, and fentanyl were assessed under FR-1 and Progressive Ratio (PR) schedules.
- Heroin's anti-nociceptive effects were evaluated using a warm water tail-withdrawal assay.
Main Results:
- Female HS rats demonstrated higher opioid intake across various conditions, including acquisition, FR-1 dose substitution, and PR procedures for oxycodone and fentanyl.
- Male rats exhibited moderate sensitivity to the anti-nociceptive effects of heroin.
Conclusions:
- Genetically diverse female HS rats self-administer opioids at significantly higher rates than their male counterparts.
- Sex is a critical biological variable influencing opioid intake and seeking behavior.
