ABSTRACT. It is known that water deprivation or injection of hypertonic saline induces anorexia. The present study examined the possible involvement of vasopressin in the suppression of food intake during high plasma osmolality. Intraperitoneal injection of vasopr essin (20 µg/kg) into male rats significantly suppressed food intake for 1 hr. This anorectic effect of vasopressin was reversed by simultaneous injection of a peptide antagonist for V 1 receptor (40 µg/kg), but not for V 2 receptor (40 µg/kg). Intraperitoneal injection of hypertonic saline (20% NaCl, 2 ml/kg) similarly suppressed food intake for 2 hr, which was associated with a transient increase in plasma vasopressin concentrations. This hypertonic saline-induced suppression of food intake was blocked by a V 1 receptor antagonist. Vasopressin (40 ng/2 µl) directly administered into the third ventricle of the brain also suppressed food intake for 1 hr. These results suggest that vasopressin participates in the suppression of food intake during high plasma osmolality, the action of which is mediated by V 1 receptors in the brain. KEY WORDS: food intake, plasma osmolality, vasopressin, V 1 receptor.J. Vet. Med. Sci. 66(8): 951-955, 2004 The mechanisms regulating appetite attract attention in recent years due to the increasing risks of appetite disorders, obesity and related metabolic diseases [25,26]. Appetite is recognized to be primarily controlled by the hypothalamus and many other factors are involved in the regulation; including peptides derived from peripheral tissues such as leptin [12] and ghrelin [19], as well as energy substrates such as glucose and fatty acids [9]. In addition, it has been suggested that food intake is also influenced by plasma osmolality and volume. For example, during high plasma osmolality caused by water deprivation [4] or injection of hypertonic saline [8], food consumption is decreased. Although the mechanism underlying the suppression of food intake by high plasma osmolality is not well understood, vasopressin might be involved because intraperitoneal injection of vasopressin has been shown to decrease food consumption in rats [18].The secretion of vasopressin is controlled by plasma osmolality and also affected by blood pressure, blood volume, angiotensins and stress [17]. Vasopressin stimulates water absorption in renal collecting ducts, raises blood pressure and elicits corticotropin (ACTH) release from the anterior pituitary synergistically with corticotrophin-releasing hormone (CRH) from the hypothalamus [17,22,23]. There are three vasopressin receptors that mediate vasopressin effects, i.e., V 1a , V 1b and V 2 receptors [1]. V 1 receptors are localized in both the central nervous system and peripheral tissues [2,10,21], while V 2 receptors are primarily localized in the kidney where they mediate the antidiuretic effect of vasopressin [21]. The anorectic effect of exogenously administered vasopressin was shown to be reversed by a V 1 receptor antagonist [18].In the present study, to elucidate whether endogeno...