Pre-quit nicotine decreases nicotine self-administration and attenuates cue- and drug-induced reinstatement.

Abstract

Administration of smoking cessation medications in anticipation of a nominated quit date can promote abstinence. How this occurs is not widely understood, but may be due to the disruption of contingencies between smoking behaviour and acute drug effects. The aim of this study was to explore this relationship, we examined the effect of pre-quit nicotine replacement therapy on susceptibility to relapse in an animal model of nicotine dependence. Rats were trained to intravenously self-administer nicotine across 20 days. Continuous low-dose nicotine was administered via a mini-osmotic pump either across the last 7 days of self-administration and across 6 days of extinction, or across extinction only. Cue- and drug-induced reinstatements of responding were then measured with mini-pumps retained, the day after mini-pump removal or one week later. Pre-quit nicotine administration markedly reduced self-administration across the last days of training as the response, and its associated cues, no longer reliably predicted an acute drug effect. Pre-quit, but not post-quit, nicotine administration significantly attenuated cue-induced reinstatement once mini-pumps were removed, indicating that the contingency disruption across training reduced the conditioned reinforcing properties of the cue at test. Both pre-quit and post-quit nicotine attenuated nicotine-primed reinstatement. Together these results suggest that administration of a nicotine replacement prior to a nominated quit date may enhance resistance to relapse via disruption of the contingency between a response, its associated cues, and a rewarding nicotine effect.