δオピオイド受容体アゴニストKNT-127はマウスの睡眠を抑制する

抄録

Sleep is closely related with mental health, and affected by drug therapy in psychiatric disorders, and vice versa. The delta opioid receptor (DOR) agonist KNT-127 has been reported to have anxiolytic effects. Unlike benzodiazepines, KNT-127 has no side effects such as dizziness and amnesia. However, its effects on sleep have not been studied. In the present study, we investigated the effects of KNT-127 on sleep in the light period in mice. The vigilance states (e.g., wakefulness, rapid eye movement (REM) and non-REM sleep) of the ddY-mice (6-10 weeks) were classified based on the hippocampal local field potential (LFP) and neck muscle electromyogram. KNT-127 (3-30 mg/kg, i.p.) dose-dependently decreased the mean REM and non-REM sleep period, and prolonged the mean wakefulness period during 5 hr after its injection. At the wakefulness and REM sleep periods after the KNT-127 treatment, the gamma power and theta peak frequency were increased in the hippocampal LFP, suggesting that KNT-127 enhanced the neuronal activities. Pre-treatment of naltrindole (10 mg/kg, s.c.), a DOR antagonist, prevented the KNT-127-induced decrease in non-REM, but not REM, sleep. Naltrindole alone did not influence the vigilance states. Together, KNT-127 increased wakefulness by decreasing non-REM and REM sleep via DOR-dependent and -independent mechanisms, respectively.