Multiple Risk Factors Precipitate Smoking Relapse: a Demonstration Using a Rat Model of Nicotine Addiction

Abstract

Relapse to drug addiction behavior in abstinent subjects could be attributable to re-exposure to relevant environments (i.e., environmental cues), drug priming, and stressful life events. In particular, it is common for the abstinent subjects to be imposed with more than one risk factors at any social circumstance. Using a rat model of nicotine addiction, we demonstrated the behavioral effect of exposure to a combination of risk factors on relapse to nicotine-seeking behavior. Male Sprague-Dawley rats were trained to press a level to intravenously self-administer nicotine at a unit dose of 0.03 mg/kg/infusion. In the daily 60-min session, an auditory/visual stimulus was paired with each nicotine infusion so that the stimulus become a nicotine-conditioned cue. After the administration responses were extinguished without nicotine infusion, the reinstatement tests were conducted under five conditions: cue representation, nicotine priming, stress, cue/priming, and cue/stress. The results showed that nicotine priming, pharmacological stressor and re-presentation of the cue respectively reinstated lever responses. The combined presentation of these factors seemed to produce stronger effect. These laboratory findings confirmed the motivational effect of re-exposure to nicotine-associated environmental cues, nicotine priming and confrontation with stressful life events in abstinent smokers. This work would support for behavioral management, in addition to medications, to eliminate exposure to these risk factors.