{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:47:17Z","timestamp":1793400437744,"version":"4.5.0"},"reference-count":77,"publisher":"Society for Neuroscience","issue":"42","license":[{"start":{"date-parts":[[2011,4,20]],"date-time":"2011-04-20T00:00:00Z","timestamp":1303257600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2010,10,20]]},"abstract":"<jats:p>The role of GABA<jats:sub>B<\/jats:sub>receptors in sleep is still poorly understood. GHB (\u03b3-hydroxybutyric acid) targets these receptors and is the only drug approved to treat the sleep disorder narcolepsy. GABA<jats:sub>B<\/jats:sub>receptors are obligate dimers comprised of the GABA<jats:sub>B2<\/jats:sub>subunit and either one of the two GABA<jats:sub>B1<\/jats:sub>subunit isoforms, GABA<jats:sub>B1a<\/jats:sub>and GABA<jats:sub>B1b<\/jats:sub>. To better understand the role of GABA<jats:sub>B<\/jats:sub>receptors in sleep regulation, we performed electroencephalogram (EEG) recordings in mice devoid of functional GABA<jats:sub>B<\/jats:sub>receptors (<jats:italic>1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) or lacking one of the subunit 1 isoforms (<jats:italic>1a<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>1b<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>). The distribution of sleep over the day was profoundly altered in<jats:italic>1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice, suggesting a role for GABA<jats:sub>B<\/jats:sub>receptors in the circadian organization of sleep. Several other sleep and EEG phenotypes pointed to a more prominent role for GABA<jats:sub>B1a<\/jats:sub>compared with the GABA<jats:sub>B1b<\/jats:sub>isoform. Moreover, we found that GABA<jats:sub>B1a<\/jats:sub>protects against the spontaneous seizure activity observed in<jats:italic>1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. We also evaluated the effects of the GHB-prodrug GBL (\u03b3-butyrolactone) and of baclofen (BAC), a high-affinity GABA<jats:sub>B<\/jats:sub>receptor agonist. Both drugs induced a state distinct from physiological sleep that was not observed in<jats:italic>1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. Subsequent sleep was not affected by GBL whereas BAC was followed by a delayed hypersomnia even in<jats:italic>1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>and<jats:italic>2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. The differential effects of GBL and BAC might be attributed to differences in GABA<jats:sub>B<\/jats:sub>-receptor affinity. These results also indicate that all GBL effects are mediated through GABA<jats:sub>B<\/jats:sub>receptors, although these receptors do not seem to be involved in mediating the BAC-induced hypersomnia.<\/jats:p>","DOI":"10.1523\/jneurosci.3145-10.2010","type":"journal-article","created":{"date-parts":[[2010,10,20]],"date-time":"2010-10-20T17:39:45Z","timestamp":1287596385000},"page":"14194-14204","source":"Crossref","is-referenced-by-count":94,"title":["Differential Effects of GABA<sub>B<\/sub>Receptor Subtypes, \u03b3-Hydroxybutyric Acid, and Baclofen on EEG Activity and Sleep 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