Neuropeptide Y promotes sleep and inhibits ACTH and cortisol release in young men

Anxiolytic and sedative effects of neuropeptide Y (NPY) are thought to invo lve inhibition of corticotropin-releasing hormone (CRH). Enhanced secretion of CRH plays a critical role in the pathophysiology of major depression, c haracterized by sleep disturbances, anxiety and loss of appetite. We examin ed for the first time in young men effects of intravenous injections of NPY (4x50 or 100 mu g, n=9 and 11, respectively, at 22.00, 23.00, 24.00 and 01 .00 compared to saline) on the sleep electroencephalogram (EEG; recorded fr om 23.00 to 07.00) and nocturnal secretion of adrenocorticotrophic hormone (ACTH), cortisol, growth hormone (GH), prolactin and leptin. Repeated measu res MANOVA showed that ACTH secretion during the first half of the night wa s reduced by the lower dose of NPY only (F=8.7, p<0.05), while cortisol sec retion during the second half of the night was reduced regardless of the do se (F=7.9, p<0.05). Regardless of the dose, NPY enhanced sleep period time and stage 2 sleep (F=12.8 and 5.4, each p<0.05), and also reduced sleep lat ency and time awake (F=4.9 and 4.4, each p<0.05) and modulated REM sleep. I n summary, NPY promotes sleep and inhibits the hypothalamo-pituitary-adreno cortical (HPA) axis in humans, pointing to a possible role of NPY agonists for the development of novel treatment strategies for affective disorders. (C) 2000 Elsevier Science Ltd. All rights reserved.