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GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites for GABA in the CNS and regulates GA BAergic 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 regula tion, we observed the sleep behaviors of mice treated by NO711, 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 quitc diffcred from those induced by zolpidem, a widely used hypnotic that binds preferentially to αl GABAA receptor.NO711 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.Immunohis tochemistry 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 tuberomanmnillary nucleus (TMN), lateral hypothalamns (LH),and locus ceruleus (LC), were decreased by NO-711 treatment.These results indicated that NO-711 induced NREM sleep by mod ulating the sleep-wake related nucleus.Suggests GAT1 may be a potential target for hypnotic in treatment of insomnia.