The effects of nicotine on sleep in female C57BL/6J mice.

Sleep disturbances during nicotine withdrawal are well-documented and strongly linked to relapse. While previous studies, including our lab's work in male mice (Mathews & Stitzel, 2019), have characterized the effects of nicotine exposure and abstinence on sleep, potential sex differences remain unclear. Given that biological sex influences both nicotine addiction and sleep regulation, understanding its role in withdrawal-induced sleep disturbances is critical. This study examines the effects of nicotine exposure and abstinence on sleep in female C57BL/6 J mice using EEG/EMG recordings to assess sleep architecture and spectral power. Mice underwent chronic oral nicotine self-administration followed by abstinence, allowing for a detailed analysis of NREM and REM sleep metrics, sleep fragmentation, and EEG spectral power. Nicotine access significantly reduced total sleep time and NREM sleep while increasing sleep fragmentation and REM bout duration. During abstinence, females exhibited persistent NREM fragmentation, a hallmark of withdrawal-induced sleep disruption linked to hyperarousal and relapse vulnerability. Additionally, spectral power analyses revealed that nicotine exposure and abstinence strongly influenced EEG spectral patterns when examined by vigilance state, with the most pronounced alterations occurring during NREM and REM sleep. Compared to males from our previous study, female mice displayed a more robust sleep fragmentation phenotype during abstinence, suggesting heightened sensitivity to withdrawal-induced sleep disturbances. These findings emphasize the importance of sex-specific mechanisms in nicotine addiction and support targeting withdrawal-related sleep disruptions to improve relapse prevention strategies for nicotine use disorder.