GABA transporter subtype 1(GAT1) constructs high affinity reuptake sites for GABA in the CNS and regulates GABAergic transmission.Compounds that inhibit GAT1 are targets for epilepsy treatment.Sedation has been reported as a side effect of these agents,indicating possible sedative or hypnotic potential.To elucidate the role of GAT1 in sleep-wake regulation,we observed the sleep behaviors of mice treated by NO-711,a selective GAT1 inhibitor.The current data reveal that NO-711(10 mg·kg-1) causes a marked enhancement of EEG power density in theta(4-10 Hz) and the high frequency range EEG activity during the wakefulness and REM sleep,which were quite differed from those induced by zolpidem,a widely used hypnotic that binds preferentially to α1 GABAA receptor.NO-711 administered ip at doses of 1,3 or 10 mg·kg-1 significantly increased the amount of non-rapid eye movement(non-REM,NREM) sleep and shortened the sleep latency to NREM sleep.NO-711 at doses of 3 and 10 mg·kg-1 increased the number of NREM bouts and prolonged the mean duration at 10 mg·kg-1,and increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness.NO-711 did not affect the architecture of REM sleep.Immunohistochemistry study showed that NO-711 dose-dependently increased c-Fos expression in neurons of the ventrolateral preoptic area(VLPO) and median preoptic nucleus(MnPO),which have been proposed to have a role in sleep-related processes.While the c-Fos expression in wakefulness-related processes nucleus,such as tuberomammillary nucleus(TMN),lateral hypothalamus(LH),and locus ceruleus(LC),were decreased by NO-711 treatment.These results indicated that NO-711 induced NREM sleep by modulating the sleep-wake related nucleus.Suggests GAT1 may be a potential target for hypnotic in treatment of insomnia. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites for GABA in the CNS and regulates GABAergic transmission. Compounds that inhibit GAT1 are targets for epilepsy treatment. Redistry has been reported as a side effect of these agents, indicating possible sedative or hypnotic potential .To elucidate the role of GAT1 in sleep-wake regulation, we observed the sleep behaviors of mice treated by NO-711, a selective GAT1 inhibitor. The current data reveal that NO-711 (10 mg · kg-1) causes a marked enhancement of EEG power density in theta (4-10 Hz) and the high frequency range EEG activity during the wakefulness and REM sleep, which were quite differed from those induced by zolpidem, a widely used hypnotic that binds preferentially to α1 GABAA receptor. NO -711 administered ip at doses of 1,3 or 10 mg · kg-1 significantly increased the amount of non-rapid eye movement (non-REM, NREM) sleep and shortened the sleep latency to NREM sleep. NO-711 at doses of 3 and 10 mg · kg-1 increased the n umber of NREM bouts and prolonged the mean duration at 10 mg · kg-1, and increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. NO-711 did not affect the architecture of REM sleep. Immunohistochemistry study showed that NO-711 dose-dependently increased c-Fos expression in neurons of the ventrolateral preoptic area (VLPO) and median preoptic nucleus (MnPO), which have been proposed to have a role in sleep-related processes. Whilst the c- Fos expression in wakefulness-related processes nucleus, such as tuberomammillary nucleus (TMN), lateral hypothalamus (LH), and locus ceruleus (LC), were decreased by NO-711 treatment.These results that NO-711 induced NREM sleep by modulating the sleep-wake related nucleus. Suggests GAT1 may be a potential target for hypnotic in treatment of insomnia.