Exploring the Pharmacodynamic Properties of Fentanyl: A Comparative Analysis of Intraperitoneal Injection and Vapor Self-Administration in a Mouse Model of Substance Use Disorders

Introduction: Amidst the ongoing opioid crisis, there is a critical need for research to comprehend the underlying mechanisms of substance use disorders and investigate potential treatments. While intravenous fentanyl administration stands as a gold standard in mouse studies, it presents challenges such as difficulty in placing catheters in mice and frequent catheter failure, hindering experimental progress. This study introduces an innovative vapor self-administration model for fentanyl delivery, aiming to evaluate the pharmacodynamic properties of fentanyl when administered passively through vapor.

Methods: A series of experiments were conducted involving three groups of mice: intraperitoneal injection of fentanyl, passive vapor self-administration using equivalent doses, and a control group for each experimental group. The analgesic effect of fentanyl was assessed through the hot plate test over a period ranging from 5 to 120 minutes. Mice were placed on a hot plate, and specific signs were evaluated within a 30-second window following fentanyl administration.

Results: The analgesic effect of fentanyl was examined using the hot plate test, and a dose-response curve was constructed, revealing comparable responses in mice for both intraperitoneal injection and passive vapor self-administration of fentanyl.

Conclusions: The utilization of the vapor self-administration model represents a promising advancement in the field. Our data illuminate this method from a pharmacological perspective, demonstrating a robust analgesic effect of fentanyl through vapor self-administration, comparable to intraperitoneal administration. Further experiments are warranted to explore the full range of properties associated with this methodology.