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GABA transporter-1 inhibitor NO-711 alters the EEG power spectra and enhances non-rapid eye movement sleep during the active phase in mice.
- Source :
-
European Neuropsychopharmacology . Apr2014, Vol. 24 Issue 4, p585-594. 10p. - Publication Year :
- 2014
-
Abstract
- Abstract: 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 often used for the treatment of epilepsy; however sedation has been reported as a side effect of these agents, indicating potential sedative and/or hypnotic uses for these compounds. In the current study, we observed the sleep behaviors of mice treated with NO-711, a selective GAT1 inhibitor, in order to elucidate the role of GAT1 in sleep–wake regulation during the active phase. The data revealed that NO-711 at a high dose of 10mg/kg caused a marked enhancement of EEG activity in the frequency ranges of 3–25Hz during wakefulness as well as rapid eye movement (REM) sleep. During the non-REM (NREM) sleep, NO-711 (10mg/kg) elevated EEG activity in the frequency ranges of 1.5–6.75Hz. Similar changes were found in mice treated with a low dose of 3mg/kg. NO-711 administered i.p. at a dose of 1, 3 or 10mg/kg significantly shortened the sleep latency of NREM sleep, increased the amount of NREM sleep and the number of NREM sleep episodes. NO-711 did not affect the sleep latency and the amount of REM sleep. NO-711 dose-dependently increased c-Fos expression in sleep-promoting nucleus of the ventrolateral preoptic area and median preoptic area. However, c-Fos expression was decreased in the wake-promoting nuclei, tuberomammillary nucleus and lateral hypothalamus. These results indicate that NO-711 can increase NREM sleep in mice. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0924977X
- Volume :
- 24
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- European Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 94896756
- Full Text :
- https://doi.org/10.1016/j.euroneuro.2013.09.002