A novel melatonin derivative modulates sleep-wake cycle in rats.
The aim of this study was to evaluate, in comparison with melatonin (MLT), the effects of a novel 2-melatonin derivative, having a 2-trifluoromethyl group (MLTD) on the sleep-wake cycle in freely behaving rats. Doses of MLTD (100, 300 and 500 nmol/100 microl saline) or MLT (500 nmol/100 microl saline) replaced the i.c.v. infusion of saline during the diurnal infusion period (7:00-17:00). Diurnal infusion of MLTD significantly (P < 0.05) increased NREM sleep at doses of 300 and 500 nmol during the second 4-h time interval of the light period and the lowest dose showed delayed effects on NREM sleep in the third 4-h time interval. However, REM sleep was only increased significantly at the dose of 500 nmol. The infusion of MLT did not have effects on REM sleep but significantly increased NREM sleep. These findings support the notion that MLTD diurnal infusion into the third ventricle produces soporific effects dose-dependently and more potently than MLT. Thus, MLTD may play an important role in studies of sleep.
Akanmu
Moses A
MA
Department of Biosystem Regulation, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, 101-0062, Japan.
Songkram
Chalermkiat
C
Kagechika
Hiroyuki
H
Honda
Kazuki
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D007276:Injections, Intraventricular; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D012890:Sleep / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects*
D008550:Melatonin