The Effects of Nicotine on Conditioning, Extinction, and Reinstatement in Humans Using a Virtual Reality Conditioned Place Preference Paradigm

Despite an abundance of evidence illustrating the harmful effects of nicotine use, only a small percentage of users successfully quit (Messer et al., 2008). Moreover, current treatments for nicotine cessation produce only a slight increase in the likelihood of successfully quitting, which emphasizes the need for more effective strategies that facilitate smoking cessation (Hopkins et al., 2001). Several studies suggest that difficulty in controlling nicotine use behaviors results from nicotine’s ability to enhance the motivating function of cues associated with obtaining rewards. These studies indicate that it is of value to understand the behavioral and neuropharmacological mechanisms by which nicotine enhances responding for conditioned rewards. Unfortunately, despite ample non-human studies, there is a paucity of literature examining nicotine’s ability to enhance reward responding in humans. Thus, in order to better understand the reward mechanisms that underlie the risk for becoming dependent, the aim of the current study was to examine nicotine’s effects on conditioning, extinction, and reinstatement in humans. Using a novel virtual reality translation of the hallmark conditioned place preference paradigm to investigate the aforementioned objectives, our main findings suggest that nicotine (1) increases the sensitivity of reward properties by enhancing the strength of food-reward conditioning, (2) delays the rate of extinction of conditioned preferences, and (3) increases the reinstatement of previous conditioning. These findings demonstrate the efficacy of utilizing the virtual conditioned place preference paradigm in understanding the behavioral mechanisms by which nicotine enhances responding for conditioned rewards, and provide insight into how nicotine can be particularly resistant to treatment. Importantly, these data provide key information for future work aimed at increasing the understanding of how conditioning paradigms can help treat and prevent substance dependences