Differential effects of GABAB receptor subtypes, {gamma}-hydroxybutyric Acid, and Baclofen on EEG activity and sleep regulation.

Détails

Ressource 1Télécharger: BIB_DAB7E89984ED.P001.pdf (2971.71 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_DAB7E89984ED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Differential effects of GABAB receptor subtypes, {gamma}-hydroxybutyric Acid, and Baclofen on EEG activity and sleep regulation.
Périodique
The Journal of neuroscience : the official journal of the Society for Neuroscience
Auteur(s)
Vienne J., Bettler B., Franken P., Tafti M.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
20/10/2010
Peer-reviewed
Oui
Volume
30
Numéro
42
Pages
14194-14204
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The role of GABA(B) receptors in sleep is still poorly understood. GHB (γ-hydroxybutyric acid) targets these receptors and is the only drug approved to treat the sleep disorder narcolepsy. GABA(B) receptors are obligate dimers comprised of the GABA(B2) subunit and either one of the two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b). To better understand the role of GABA(B) receptors in sleep regulation, we performed electroencephalogram (EEG) recordings in mice devoid of functional GABA(B) receptors (1(-/-) and 2(-/-)) or lacking one of the subunit 1 isoforms (1a(-/-) and 1b(-/-)). The distribution of sleep over the day was profoundly altered in 1(-/-) and 2(-/-) mice, suggesting a role for GABA(B) receptors in the circadian organization of sleep. Several other sleep and EEG phenotypes pointed to a more prominent role for GABA(B1a) compared with the GABA(B1b) isoform. Moreover, we found that GABA(B1a) protects against the spontaneous seizure activity observed in 1(-/-) and 2(-/-) mice. We also evaluated the effects of the GHB-prodrug GBL (γ-butyrolactone) and of baclofen (BAC), a high-affinity GABA(B) receptor agonist. Both drugs induced a state distinct from physiological sleep that was not observed in 1(-/-) and 2(-/-) mice. Subsequent sleep was not affected by GBL whereas BAC was followed by a delayed hypersomnia even in 1(-/-) and 2(-/-) mice. The differential effects of GBL and BAC might be attributed to differences in GABA(B)-receptor affinity. These results also indicate that all GBL effects are mediated through GABA(B) receptors, although these receptors do not seem to be involved in mediating the BAC-induced hypersomnia.

Mots-clé
Anesthetics, Intravenous/pharmacology, Animals, Baclofen/pharmacology, Behavior, Animal/drug effects, Delta Rhythm/drug effects, Electrodes, Implanted, Electroencephalography/drug effects, Electromyography, Epilepsy/genetics, Epilepsy/physiopathology, GABA Agonists/pharmacology, Male, Mice, Mice, Inbred BALB C, Mice, Knockout, Receptors, GABA-B/drug effects, Receptors, GABA-B/genetics, Sleep/drug effects, Sleep Deprivation/physiopathology, Sleep, REM/drug effects, Sodium Oxybate/pharmacology, Theta Rhythm/drug effects
Pubmed
Web of science
Open Access
Oui
Création de la notice
08/02/2011 11:30
Dernière modification de la notice
09/05/2019 2:05
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