Abstract

Relapse in nicotine addiction is often influenced by environmental cues, drug re-exposure, and stress. These factors frequently co-occur, increasing the likelihood of relapse in abstinent individuals. Using a rat model of nicotine addiction, we examined how combined risk factors impact relapse behavior. Male Sprague-Dawley rats were conditioned to self-administer nicotine through lever presses (0.03 mg/kg/infusion) paired with auditory/visual cues. Following extinction of these responses, we assessed relapse through five conditions: cue re-exposure, nicotine priming, stress, cue/priming, and cue/stress. Results indicated that each factor—nicotine priming, stress, and cue individually reinstated lever responses, with combined exposures producing a stronger effect. These findings underscore the powerful role of nicotine-related cues, drug priming, and stress in relapse, supporting behavioral strategies alongside pharmacological interventions to minimize exposure to these triggers.