The GABAA agonist THIP produces slow wave sleep and reduces spindling activity in NREM sleep in humans
- PMID: 9151364
- DOI: 10.1007/s002130050241
The GABAA agonist THIP produces slow wave sleep and reduces spindling activity in NREM sleep in humans
Abstract
Recent studies in the rat demonstrated that systemic administration of muscimol and THIP, both selective GABAA receptor agonists, elevates slow wave activity in the EEG during non-rapid eye movement (NREM) sleep. In this placebo-controlled study, we assessed the influence of an oral dose of 20 mg THIP on nocturnal sleep in young healthy humans. Compared to placebo, THIP increased slow wave sleep by about 25 min. Spectral analysis of the EEG within NREM sleep revealed significant elevations in the lower frequencies (< 8 Hz) and reductions in the spindle frequency range (approximately 10-16 Hz). In accordance with previous findings in the rat, these data imply that GABAA agonists promote deep NREM sleep, without suppressing REM sleep. These effects are opposite to those induced by agonistic modulators of GABAA receptors such as benzodiazepines and are at variance with established mechanisms according to which GABAA agonists and modulatory agonists would have similar effects. The sleep response to GABAA agonists is highly similar to that evoked by sustained wakefulness, suggesting that GABAA receptors may be implicated in the homeostatic regulation of sleep.
Similar articles
-
The GABAA agonist THIP (gaboxadol) increases non-REM sleep and enhances delta activity in the rat.Neuroreport. 1996 Sep 2;7(13):2241-5. doi: 10.1097/00001756-199609020-00036. Neuroreport. 1996. PMID: 8930997
-
Role of GABAA receptors in the regulation of sleep: initial sleep responses to peripherally administered modulators and agonists.Sleep. 1999 Feb 1;22(1):33-42. doi: 10.1093/sleep/22.1.33. Sleep. 1999. PMID: 9989364 Review.
-
The GABAA receptor agonist THIP alters the EEG in waking and sleep of mice.Neuropharmacology. 2005 Apr;48(5):617-26. doi: 10.1016/j.neuropharm.2004.12.015. Neuropharmacology. 2005. PMID: 15814097
-
The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A)delta-subunit-containing receptors.Eur J Neurosci. 2007 Mar;25(6):1893-9. doi: 10.1111/j.1460-9568.2007.05455.x. Epub 2007 Apr 4. Eur J Neurosci. 2007. PMID: 17408425
-
Extrasynaptic GABAA receptors are critical targets for sedative-hypnotic drugs.J Clin Sleep Med. 2006 Apr 15;2(2):S12-8. J Clin Sleep Med. 2006. PMID: 17557502 Review.
Cited by
-
An examination of sleep spindle metrics in the Sleep Heart Health Study: superiority of automated spindle detection over total sigma power in assessing age-related spindle decline.BMC Neurol. 2023 Oct 6;23(1):359. doi: 10.1186/s12883-023-03376-3. BMC Neurol. 2023. PMID: 37803266 Free PMC article.
-
Paradoxical pharmacological dissociations result from drugs that enhance delta oscillations but preserve consciousness.Commun Biol. 2023 Jun 20;6(1):654. doi: 10.1038/s42003-023-04988-8. Commun Biol. 2023. PMID: 37340024 Free PMC article. Review.
-
Mutual interaction between visual homeostatic plasticity and sleep in adult humans.Elife. 2022 Aug 16;11:e70633. doi: 10.7554/eLife.70633. Elife. 2022. PMID: 35972073 Free PMC article.
-
The GABAA receptor modulator zolpidem augments hippocampal-prefrontal coupling during non-REM sleep.Neuropsychopharmacology. 2023 Mar;48(4):594-604. doi: 10.1038/s41386-022-01355-9. Epub 2022 Jun 18. Neuropsychopharmacology. 2023. PMID: 35717464 Free PMC article.
-
Better Sleep at Night: How Light Influences Sleep in Drosophila.Front Physiol. 2020 Sep 4;11:997. doi: 10.3389/fphys.2020.00997. eCollection 2020. Front Physiol. 2020. PMID: 33013437 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources