NDLI: Diazepam-induced changes in sleep: role of the alpha 1 GABA(A) receptor subtype.

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Diazepam-induced changes in sleep: role of the alpha 1 GABA(A) receptor subtype.

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Diazepam-induced changes in sleep: role of the alpha 1 GABA(A) receptor subtype.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kopp, C. Deboer, T. Tobler, I. Rudolph, U.
Description	Author Affiliation: Tobler I ( Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. tobler@pharma.unizh.ch);
Abstract	Ligands acting at the benzodiazepine (BZ) site of gamma-aminobutyric acid type A (GABA(A)) receptors currently are the most widely used hypnotics. BZs such as diazepam (Dz) potentiate GABA(A) receptor activation. To determine the GABA(A) receptor subtypes that mediate the hypnotic action of Dz wild-type mice and mice that harbor Dz-insensitive alpha1 GABA(A) receptors [alpha1 (H101R) mice] were compared. Sleep latency and the amount of sleep after Dz treatment were not affected by the point mutation. An initial reduction of rapid eye movement (REM) sleep also occurred equally in both genotypes. Furthermore, the Dz-induced changes in the sleep and waking electroencephalogram (EEG) spectra, the increase in power density above 21 Hz in non-REM sleep and waking, and the suppression of slow-wave activity (SWA; EEG power in the 0.75- to 4.0-Hz band) in non-REM sleep were present in both genotypes. Surprisingly, these effects were even more pronounced in alpha1(H101R) mice and sleep continuity was enhanced by Dz only in the mutants. Interestingly, Dz did not affect the initial surge of SWA at the transitions to sleep, indicating that the SWA-generating mechanisms are not impaired by the BZ. We conclude that the REM sleep inhibiting action of Dz and its effect on the EEG spectra in sleep and waking are mediated by GABA(A) receptors other than alpha1, i.e., alpha2, alpha3, or alpha5 GABA(A) receptors. Because alpha1 GABA(A) receptors mediate the sedative action of Dz, our results provide evidence that the hypnotic effect of Dz and its EEG 'fingerprint' can be dissociated from its sedative action.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Diazepam Pharmacology Hypnotics And Sedatives Receptors, GABA-A Physiology Drug Effects Animals Electroencephalography Mice Sleep, REM Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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