Fentanyl administration in mice: A comparative study of method vapor self-administration vs intraperitoneal injection

Introduction: The synthetic opioid crisis, particularly involving fentanyl, has led to a dramatic surge in overdose deaths in the United States, with over 70,000 fatalities in 2021. Oklahoma reflects this trend, reporting 1,196 overdose deaths in 2022—a record rate of 30 per 100,000 residents. Fentanyl-related deaths in the state skyrocketed from 47 in 2019 to 300 in 2022. This crisis underscores the urgent need for advanced research into opioid use disorders and treatments. While the intravenous self-administration model in rodents is the current gold standard for studying opioid addiction, it presents challenges such as catheter placement difficulties and maintenance issues. To overcome these obstacles, a vapor self-administration model for fentanyl delivery is being considered as a promising alternative, potentially enhancing research efficiency and providing new insights into addiction mechanisms and therapeutic approaches.

Objectives: To determine if the pharmacodynamic of fentanyl via vapor self-administration was comparable to IP administration.

Methods:
•96 naive mice were divided into 12 groups
•Fentanyl was administered through IP injections and vapor routes at equipotent doses
•The analgesic effect of fentanyl was evaluated using the hot-plate test

Conclusion: Hot-plate assays revealed equivalent analgesic effects in mice following fentanyl administration via intraperitoneal (IP) injection and passive vapor self-administration routes. The vapor self-administration paradigm represents a significant innovation in preclinical addiction research, offering enhanced translational potential for investigating substance use disorders.