Title: Wireless intravenous self-administration: a novel approach to preclinical animal models of substance use disorders

Author: Collin D. Teague

Area of Concentration: Basic, Clinical, and Translational Research

Keywords: Addiction, preclinical animal models, fentanyl self-administration

Background: Intravenous self-administration (IVSA) is regarded as the gold standard rodent model of substance use disorders (SUDs). However, traditional IVSA experiments require a tether for drug delivery and are performed within operant chambers that limit access to environmental enrichment, socialization, and alternative behaviors. Therefore, preclinical models often overlook environmental factors that influence the acquisition, escalation, and relapse of drug use in humans. To tackle this limitation, we aim to develop a wireless infusion device and conduct the first-ever studies on rodent IVSA behavior within a naturalistic environment. 

Objective: Aim 1: Develop a wireless infusion device and validate drug delivery in vivo. Aim 2: Assess the impact of wearing the device on ambulatory and reward-seeking behavior. Aim 3: Compare fentanyl IVSA behavior between the wireless and tethered approaches. 

Methods: The device consists of a micro-infusion pump, drug reservoir, and battery encapsulated in a 3D-printed case with a catheter implanted in the jugular vein. We validated intravenous drug delivery in vivo using fentanyl-induced respiratory depression and fiber photometry in the ventral tegmental area (VTA). We assessed the impact of wearing the device on animal behavior using open field and sucrose self-administration. Lastly, we aim to compare fentanyl IVSA behavior between the tethered and wireless approaches.

Results: We confirmed intravenous drug delivery by demonstrating that a wireless infusion of fentanyl significantly reduces oxygen saturation and calcium transients within the VTA. Wearing the device decreased locomotion in male and female rats, but has no effect on operant sucrose self-administration. Lastly, we show wireless intravenous fentanyl self-administration in a proof-of-concept experiment.

Conclusion: Here, we developed wireless intravenous infusion technology for rats. We envision that this technology will enable studies on how environmental factors influence drug use, improve the translational value of preclinical SUD models, and ultimately enhance treatment discovery efforts for SUDs.