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Correction of sleep disturbances during abstinence following hypocretin-receptor antagonism in fentanyl-dependent rats.Jones, Marissa R, Sawyer, Benjamin, Schmeichel, Brooke E 25 April 2023 (has links)
Fentanyl is a potent synthetic opioid that has been shown to produce sleep disturbances, and the deterioration of sleep quality is associated with drug abuse and relapse in humans. The hypocretin/orexin neuropeptide system is a plausible pharmacological target, and dual-hypocretin antagonists such as lemborexant may mitigate sleep disturbances associated with fentanyl dependence. The current study characterizes sleep macroarchitecture (time spent asleep or awake) and microarchitecture (the number of bouts, and NREM sleep spindle characterization) prior to fentanyl vapor exposure (baseline), following one week of drug abstinence, and four weeks of drug abstinence in female and male rats. Females and males showed a reduction in the amount of time spent in rapid eye movement (REM) sleep following one week of abstinence. The pre-treatment of lemborexant the following day increased the amount of time spent in REM, compared to vehicle at both one and four weeks of abstinence. While there was no effect of fentanyl abstinence on the amount of time spent in non-rapid eye movement (NREM) sleep and wakefulness, lemborexant increased the amount time spent in NREM and decreased the amount of time spent awake. Examination of microarchitecture demonstrated a decrease in the number of NREM bouts at one week of abstinence, which lemborexant subsequently brought back to baseline levels at weeks one and four. Abstinence from fentanyl did not impact the number of NREM sleep spindles, but indicated a trend showing a decrease in intra-spindle frequency at one week of abstinence. Lemborexant, however, increased the number of spindles at weeks one and four of abstinence. Presently, findings indicate that fentanyl abstinence produces changes in sleep macroarchitecture, particularly REM sleep disruptions, which may be alleviated by lemborexant. This highlights the need for further examination of the relationship between sleep disturbances and drug abstinence, and the use of dual-hypocretin antagonists as therapeutic intervention.
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