Effects of leptin on milk consumption in food-deprived mice were investigated. In this feeding model, systemic administration of leptin reduced milk intake of mice dose-dependently. Decreases in milk intake elicited by leptin were significantly reduced by the serotonin (5-HT) synthesis inhibitor p-chlorophenylalanine (PCPA). The suppressive effects of leptin on milk intake were antagonized by the 5-HT2B/2C receptor antagonist SB206553, while the 5-HT1B receptor antagonist GR55562 and the 5-HT2A receptor antagonist ketanserin did not affect it. Our results indicated that the 5-HT depleter PCPA and the 5-HT2B/2C receptor antagonist SB206553 attenuated leptin-induced suppression of milk intake. Therefore, leptin-induced hypophagic effects may be mediated by enhancement of serotonergic neurons, resulting in activation of the 5-HT2B/2C receptor. (C) 2003 Elsevier Ireland Ltd. All rights reserved.