Submitted on May 13, 2004
Accepted on July 13, 2004
OREXIN-A DOES NOT STIMULATE FOOD INTAKE IN OLD RATS
Saeko Takano1, Setsuko Kanai2, Hiroko Hosoya2, Minoru Ohta2, Hiroshi Uematsu3, and Kyoko Miyasaka2*
1 Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan; Gerodontology, Department of Gerodontology, Division of Gerontology and Gerodontology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
2 Department of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan
3 Gerodontology, Department of Gerodontology, Division of Gerontology and Gerodontology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: miyasaka{at}tmig.or.jp.
Aging is associated with a progressive decrease in appetite and food intake. Orexins
(both A and B), expressed in specific neurons of the lateral hypothalamic area, have been
implicated in the regulation of sleep and feeding. In this study, the stimulatory effect of
intracerebroventricular administration of the orexins on food intake was compared between
young (4-month-old) and old (25-27-month-old) male Wistar rats. A stainless steel cannula was
implanted stereotactically into the left lateral ventricle. After a 7-day recovery period, different
doses (0 to 30 nmol) of orexins were injected into the left lateral ventricle without anesthesia.
Food and water consumption was measured at 1, 2, and 4 hr after injection. The protein levels
of orexin receptors (OX1R = a specific receptor for orexin-A, OX2R = a receptor for both orexin-
A and -B) in the hypothalamus were determined by Western blotting and compared between
young and old rats. Intracerebroventricular administration of orexin-A stimulated food intake in
a dose-dependent manner in young rats. However, no effects were observed at any dose in old
rats. The protein level of OX1R in the hypothalamus was significantly lower in old rats than in
young, although the protein level of OX2R was comparable between groups. The present
results indicate that the function of the orexin system is diminished in old rats. The decrease in
the OX1R protein level in the hypothalamus could be responsible for orexin-A's lack of
stimulation of food intake in old rats.
