Dual orexin receptor antagonism modulates sleep during nicotine withdrawal in female and male C57BL/6J mice.
Journal Article
Overview
abstract
Sleep disruption is a common symptom of nicotine withdrawal that contributes to relapse risk and impedes successful cessation. The orexin (hypocretin) system regulates sleep-wake states and is implicated in nicotine dependence, making it a candidate target for treating withdrawal-related sleep disturbance. This study tested whether the dual orexin receptor antagonist suvorexant modulates sleep during nicotine abstinence in female and male C57BL/6 J mice. Adult female and male C57BL/6 J mice received nicotine or saline via osmotic mini-pumps for 12 days, after which pumps were removed to induce withdrawal. Sleep-wake behavior was monitored continuously using a noninvasive piezoelectric system. During early abstinence (days 1-2), mice received suvorexant (30 mg/kg) or vehicle at light onset, and outcomes included percent sleep, total sleep time, and sleep-bout architecture (bout frequency and duration) across light and dark periods. Nicotine abstinence altered sleep across multiple metrics, with distinct patterns observed in females and males. In females on abstinence day 2, suvorexant altered early post-dose percent sleep in a nicotine-history-dependent manner, increasing sleep in nicotine-abstinent females. In males, abstinence increased total sleep and bout frequency (fragmentation), indicating a dissociation between sleep quantity and quality, and suvorexant produced only minimal effects. Together, these findings identify nicotine abstinence as the primary driver of sleep disruption and demonstrate that dual orexin receptor antagonism can acutely modulate sleep during nicotine withdrawal, while broader effects on sleep amount and sleep-bout architecture require further investigation.
