Recent findings suggest that novel associations can be learned during sleep. However, whether associative learning during sleep can alter later waking behavior and whether such behavioral changes last for minutes, hours, or days remain unknown. We tested the hypothesis that olfactory aversive conditioning during sleep will alter cigarette-smoking behavior during ensuing wakefulness. A total of 66 human subjects wishing to quit smoking participated in the study (23 females; mean age, 28.7 ± 5.2 years). Subjects completed a daily smoking diary detailing the number of cigarettes smoked during 7 d before and following a 1 d or night protocol of conditioning between cigarette odor and profoundly unpleasant odors. We observed significant reductions in the number of cigarettes smoked following olfactory aversive conditioning during stage 2 and rapid eye movement (REM) sleep but not following aversive conditioning during wakefulness (p < 0.05). Moreover, the reduction in smoking following aversive conditioning during stage 2 (34.4 ± 30.1%) was greater and longer lasting compared with the reduction following aversive conditioning during REM (11.9 ± 19.2%, p < 0.05). Finally, the reduction in smoking following aversive conditioning during sleep was significantly greater than in two separate control sleep experiments that tested aversive odors alone and the effects of cigarette odors and aversive odors without pairing. To conclude, a single night of olfactory aversive conditioning during sleep significantly reduced cigarette-smoking behavior in a sleep stage-dependent manner, and this effect persisted for several days.
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