The effect of intraperitoneal administration of leptin on short-term food intake in rats

The effects of intraperitoneal (i.p.) injection of leptin (1, 5, and 10 mug/kg) were investigated on the food consumption during a 60 min test meal in 21 h fasted rats. All doses of leptin produced significant reductions in cumulative food intake during the first 15 min and 30 min (at least, P<0.05) after administration. Similarly, i.p., but not subcutaneous (s.c.), administration of leptin (25 microg/kg) reduced food intake in 21 h fasted rats. Leptin (10 and 25 microg/kg, i.p.) did not reduce water intake in 16 h water-deprived rats, nor did leptin (25 microg/kg) produce aversion in a two-bottle conditioned taste aversion test indicating that the hypophagic effect of leptin is (i) behaviourally specific for food and not water intake, and (ii) not due to drug-induced malaise. Moreover, leptin (10 and 25 microg/kg, i.p.) did not significantly alter food intake in non-deprived rats when measured at 30 min intervals over a period of 24 h. Chemical vagotomy with capsaicin abolished the inhibitory effects of leptin (25 microg/kg, i.p) on food intake in fasted rats and suggest that the hypophagic effect is dependent on intact vagal afferent nerves. Furthermore, the hypophagia induced by leptin (10 microg/kg, i.p.) in fasted rats was not attenuated by systemic administration of the peripherally acting cholecystokinin(1) receptor antagonist, 2-naphthalenesulphanyl-L-aspartyl-2-(phenethyl) amide (2-NAP; 2 mg/kg, i.p.), indicating that the suppressant effects of leptin on food consumption are not secondary to the release of endogenous peripheral cholecystokinin.