Neurochemical regulation of sleep.
This review summarizes recent developments in the field of sleep regulation, particularly in the role of hormones, and of synthetic GABA(A) receptor agonists. Certain hormones play a specific role in sleep regulation. A reciprocal interaction of the neuropeptides growth hormone (GH)-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in sleep regulation. At least in males GHRH is a common stimulus of non-rapid-eye-movement sleep (NREMS) and GH and inhibits the hypothalamo-pituitary adrenocortical (HPA) hormones, whereas CRH exerts opposite effects. Furthermore CRH may enhance rapid-eye-movement sleep (REMS). Changes in the GHRH:CRH ratio in favor of CRH appear to contribute to sleep EEG and endocrine changes during depression and normal ageing. In women, however, CRH-like effects of GHRH were found. Besides CRH somatostatin impairs sleep, whereas ghrelin, galanin and neuropeptide Y promote sleep. Vasoactive intestinal polypeptide appears to be involved in the temporal organization of human sleep. Beside of peptides, steroids participate in sleep regulation. Cortisol appears to promote REMS. Various neuroactive steroids exert specific effects on sleep. The beneficial effect of estrogen replacement therapy in menopausal women suggests a role of estrogen in sleep regulation. The GABA(A) receptor or GABAergic neurons are involved in the action of many of these hormones. Recently synthetic GABA(A) agonists, particularly gaboxadol and the GABA reuptake inhibitor tiagabine were shown to differ distinctly in their action from allosteric modulators of the GABA(A) receptor like benzodiazepines as they promote slow-wave sleep, decrease wakefulness and do not affect REMS.
Steiger
Axel
A
Max Planck Institute of Psychiatry, Department of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich, Germany. steiger@mpipsykl.mpg.de
D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D004569:Electroencephalography / Q000187:drug effects; D004967:Estrogens / Q000502:physiology; D018755:GABA Agonists / Q000627:therapeutic use; D058785:GABA-A Receptor Agonists; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology*; D020249:Hormone Replacement Therapy; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D007555:Isoxazoles / Q000627:therapeutic use; D009479:Neuropeptides / Q000502:physiology*; D009557:Nipecotic Acids / Q000627:therapeutic use; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy / Q000503:physiopathology; D012894:Sleep Stages / Q000502:physiology*; D000078308:Tiagabine
D004967:Estrogens; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D007555:Isoxazoles; D009479:Neuropeptides; D009557:Nipecotic Acids; D003346:Corticotropin-Releasing Hormone; D013007:Growth Hormone-Releasing Hormone; C015542:gaboxadol; D000078308:Tiagabine