Genetic modulation of oxycodone self-administration trajectories: from initiation to escalating burst patterns

作者：Caleb I Hodges, Eamonn P. Duffy, Jonathan O Ward, L. H. Hale, Cove Andrews, Laura Saba, Marissa A. Ehringer, Ryan K. Bachtell · 发表于：Frontiers in Behavioral Neuroscience · 年份：2026 · DOI：10.3389/fnbeh.2026.1913370 · 研究领域：Neurotransmitter Receptor Influence on Behavior、Genetic Associations and Epidemiology、Phosphodiesterase function and regulation

Opioid Use Disorder (OUD) remains a prominent threat to global health. Genetic background influences the susceptibility of developing OUD, although specific genetic factors remain elusive. Rodent models that differ in susceptibility to escalation and dysregulation of opioid use are valuable tools to facilitate discovery of genetic pathways. Phenotypes associated with the development of OUD were compared in seven classic inbred rat strains (M520/N, WKY/NCrl, F344/NCrl, F344/Stm, LEW/Crl, LEW/SSNHsd, LE/Stm) from the Hybrid Rat Diversity Panel (HRDP). A two-phase self-administration paradigm was utilized to assess characteristics of the acquisition of oxycodone self-administration during daily 2-h sessions, and the escalation of oxycodone use during daily 12-h sessions. Genetic background influenced the acquisition of oxycodone self-administration as indicated by differences in the initiation of responding for oxycodone during each session and different amounts of oxycodone intake. We observed that escalation of oxycodone intake between-sessions was strain dependent, and the within-session distribution of oxycodone intake was strongly influenced by strain. The M520/N strain engaged in a unique pattern of intake, characterized by rapid initiation of oxycodone responding during the acquisition phase and a significant burst-like responding during escalation. Strain-dependent sex differences were also observed in several acquisition and escalation metrics. Of interest, burst respon...