A noninvasive approach to modeling cocaine self-administration in mice

BACKGROUND: Intravenous self-administration (SA) in rodents is widely regarded as the standard approach for studying the neurobiological mechanisms of drug addiction. However, its use in mice is limited by the frequent complications of intravenous catheterization, including catheter failure or occlusion. AIMS: To overcome these challenges, we developed and validated a noninvasive vapor approach for cocaine SA in mice. METHODS: In this study, mice were trained to self-administer cocaine vapor under fixed-ratio schedules (FR1 and FR3) and exposure to cocaine SA in both short-access (1 hour/day) and long-access (3 hours/day) sessions. RESULTS: Our findings show that the vaporized cocaine SA model induces robust behavioral and physiological effects consistent with cocaine use disorder. Our results demonstrated increased operant responding under higher reinforcement schedules, and the escalation of vaporized cocaine intake during extended access sessions (3 hours/day) emulates features of compulsive drug use in humans. CONCLUSIONS: Our findings show that the vaporized cocaine SA model offers a translational model to advance preclinical research and develop effective treatments. This vapor-based approach circumvents the need for catheterization, reduces animal stress, and is suitable for longitudinal studies and compatible for use with various modern neurogenetic techniques that require a tether for imaging free-moving, behaving animals (e.g., optogenetics and brain imaging).