Nicotine-induced conditioned place preferences in humans

This study investigated whether a conditioned place preference (CPP) could be established for a virtual reality (VR) room paired with nicotine. Forty-four undergraduates with nicotine use completed a 3-day, within-subjects protocol. In session 1, participants were randomly assigned to receive either a 4 mg nicotine or placebo lozenge. They were then confined to one of two visually distinct VR rooms, in which they completed three conditioning sessions. In session 2, participants crossed over to the other condition (nicotine or placebo) and the alternate VR room, then completed three conditioning sessions. Session 3 was a test session in which no lozenge was given and participants had free access to both VR rooms. Participants displayed an explicit CPP by rating the nicotine-paired room significantly more enjoyable and choosing the nicotine-paired room over the placebo-paired room in a forced-choice test of room preference. Interestingly, participants did not display an implicit CPP for the nicotine-paired room during the test session. However, greater e-cigarette dependence was positively correlated with implicit CPP for the nicotine-paired room, indicating that individuals with higher nicotine dependence spent longer in the nicotine-paired room during the test session. Intriguingly, sex differences emerged: females demonstrated implicit CPP (time spent in the nicotine-paired room), whereas males showed explicit CPP (self-reported enjoyment of and preference for the nicotine-paired room). These findings are the first demonstration that humans exhibit CPP for a nicotine-paired context and highlight the potential of the VR-CPP to reveal meaningful individual and biological differences in nicotine reward and addiction science.