Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice.
Summary of "Honokiol promotes non-rapid eye movement sleep via the benzodiazepine site of the GABA(A) receptor in mice."
BACKGROUND AND
PURPOSE:
  Houpu decoction containing honokiol has been used to treat a variety of mental disorders, including depression. Depression commonly presents alongside sleep disorders and sleep disturbances, which appear to be a major risk factor for depression. The aim of this study was to evaluate the somnogenic effect of honokiol and the mechanisms involved. EXPERIMENTAL
APPROACH:
  Honokiol was administered i.p. at 20:00 in mice. Flumazenil, an antagonist at the benzodiazepine site of the GABA(A) receptor, was administered i.p. 15 min before the injection of honokiol. The effects of honokiol were measured by electroencephalogram and -electromyogram, c-Fos expression and in vitro electrophysiology. KEY
RESULTS:
  Honokiol administered i.p. at doses of 10 and 20 mg·kg(-1) significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep and increased the amount of NREM sleep. Honokiol increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. However, honokiol had no effect on either the amount of REM sleep or electroencephalogram power density of both NREM and REM sleep. Honokiol increased c-Fos expression in the ventrolateral preoptic area (VLPO) neurons, as examined by immunostaining, and excited sleep-promoting neurons in the VLPO by whole-cell patch clamping in the brain slice. Pretreatment with flumazenil abolished the somnogenic effects and the activation of the VLPO neurons by honokiol. CONCLUSIONS AND
IMPLICATIONS:
  These results indicate that honokiol promotes NREM sleep by modulating the benzodiazepine site of the GABA(A) receptor, suggesting potential applications in the treatment of insomnia, especially for patients who experience difficulty in falling and staying asleep. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
Affiliation
Department of Pharmacology, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Shanghai Medical College of Fudan University, Shanghai 200032, China; Department of Neuroscience, Anatomy, Histology and Embryology, School of Basic Med
Journal Details
This article was published in the following journal.
Name: British journal of pharmacology
ISSN: 1476-5381
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22537192
- DOI: http://dx.doi.org/10.1111/j.1476-5381.2012.02010.x
Medical and Biotech [MESH] Definitions
Hypersomnolence, Idiopathic
A sleep disorder of central nervous system origin characterized by prolonged nocturnal sleep and periods of daytime drowsiness. Affected individuals experience difficulty with awakening in the morning and may have associated sleep drunkenness, automatic behaviors, and memory disturbances. This condition differs from narcolepsy in that daytime sleep periods are longer, there is no association with CATAPLEXY, and the multiple sleep latency onset test does not record sleep-onset rapid eye movement sleep. (From Chokroverty, Sleep Disorders Medicine, 1994, pp319-20; Psychiatry Clin Neurosci 1998 Apr:52(2):125-129)
Narcolepsy
A condition characterized by recurrent episodes of daytime somnolence and lapses in consciousness (microsomnias) that may be associated with automatic behaviors and AMNESIA. CATAPLEXY; SLEEP PARALYSIS, and hypnagogic HALLUCINATIONS frequently accompany narcolepsy. The pathophysiology of this disorder includes sleep-onset rapid eye movement (REM) sleep, which normally follows stage III or IV sleep. (From Neurology 1998 Feb;50(2 Suppl 1):S2-S7)
Gaba Modulators
Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.
Cataplexy
A condition characterized by transient weakness or paralysis of somatic musculature triggered by an emotional stimulus or physical exertion. Cataplexy is frequently associated with NARCOLEPSY. During a cataplectic attack, there is a marked reduction in muscle tone similar to the normal physiologic hypotonia that accompanies rapid eye movement sleep (SLEEP, REM). (From Adams et al., Principles of Neurology, 6th ed, p396)
Diazepam Binding Inhibitor
An 86-amino acid polypeptide, found in central and peripheral tissues, that displaces diazepam from the benzodiazepine recognition site on the gamma-aminobutyric acid receptor (RECEPTORS, GABA). It also binds medium- and long-chain acyl-CoA esters and serves as an acyl-CoA transporter. This peptide regulates lipid metabolism.
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