Differences in the appetite-stimulating effect of orexin, neuropeptide Y and ghrelin among young, adult and old rats.

Aging is associated with a progressive decrease in appetite and food intake. The appetite-stimulating peptides orexin A, neuropeptide Y (NPY) and ghrelin are known to play a critical role in food intake. In this study, the stimulatory effect of intracerebroventricular administration of these peptides on food intake was compared among young (4 months old), adult (11 months old) and old (24-27 months old) male Wistar rats. A stainless steel cannula was implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different doses of orexin A (0.25-3 nmol), NPY and ghrelin (0.03-1 nmol) were injected into the left lateral ventricle without anesthesia. Food consumption was measured at 1, 2 and 4 h after injection. We also examined the plasma levels of acylated and desacyl ghrelin in young and old rats by ELISA. Intracerebroventricular administration of orexin A and NPY stimulated food intake in young and adult rats, but no effects were observed at any dose in old rats. Ghrelin increased food intake in a dose-dependent manner in all groups, and the effect of ghrelin was reduced with advancing age. Neither the acylated nor the desacyl plasma ghrelin level differed significantly between young and old rats. In conclusion, the orexigenic effect of the peptides orexin A, NPY and ghrelin decreased in old rats, and this reduction may have been responsible for the age-related decrease in food intake.