Obestatin alters sleep in rats.

Obestatin is a recently identified peptide derived from the ghrelin gene. Ghrelin stimulates food intake whereas obestatin has an opposite effect in rats. Previous experiments in our laboratory revealed that ghrelin also induces wakefulness in rats. The aim of the present experiments was to study the effect of obestatin on sleep. Rats received intraperitoneal (n = 7; 16 or 64 microg/kg) or intracerebroventricular (i.c.v.; n = 11) injection of pyrogen-free isotonic NaCl or obestatin (1, 4 and 16 microg in a volume of 4 microl) at dark onset. Sleep-wake activity was recorded for 23 h. I.c.v. administration of 16 microg obestatin induced a significant increase (approximately 58%) in the time spent in non-rapid-eye-movement sleep (NREMS) in the first hour after the injection. This resulted from an increase in the number of NREMS episodes and shortened sleep latency. Electroencephalographic (EEG) slow-wave activity (0.5-4 Hz) was reduced by obestatin treatment. The initial increase in NREMS time was followed by a decrease in both NREMS and REMS in the second hour after the injection. Peripheral injection of obestatin did not induce significant changes in sleep in any post-injection hours. Results suggest that the sleep-promoting effect of centrally administered obestatin may be part of the behavioral manifestation of satiety elicited by the peptide. Current results confirm the finding that two regulatory peptides derived from the same gene have opposite actions in the same species.