Development of a nose-poke restricted vaporized cocaine self-administration model in mice.

The need for preclinical models that better reflect human substance use patterns has increased due to the rising misuse of electronic cigarettes (e-cigarettes) for drug inhalation. However, Self administration studies using mice in this context remain limited. To address this, we developed a self-administration model in which mice voluntarily insert their nose into a nose poke port, where vaporized cocaine passes through an airway, allowing controlled inhalation. Mice were exposed to vaporized cocaine at 50, 100, 200, and 300 mg/mL, and active nose-poke response was significantly increased compared to vehicle across concentrations, except at 300 mg/mL. At 100 mg/mL, plasma cocaine was 284 nM, with no significant sex differences detected. During extinction, active responses decreased over time and were reinstated following exposure to cocaine vapor-associated cues and cocaine priming. We also observed differences between the cocaine and vehicle groups in rewards earned, and active nose-poke responding during the progressive-ratio (PR) sessions. This model provides a preclinical approach for studying vaporized cocaine self-administration. A key advantage of this system is that it enables temporally precise, self-administered bolus delivery of drug exposure. This feature allows for improved experimental control over the timing and pattern of drug intake, facilitating investigation of the reinforcing effects of vaporized cocaine.