We have previously reported that i.p. administration of low microgram doses of leptin produces a short lasting decrease in food intake in rats that had been fasted for between 21 and 22h by a vagally mediated mechanism and suggested that leptin released from the stomach during a meal may play a role as a short-term peripheral satiety factor (Patel et al., 2002, 2003). In the present study we sought to extend these observations by investigating the effects of i.p. administration of low microgram doses of leptin on (a) operant food intake in rats that had been fasted for 5h, and (b) food intake in non-deprived rats measured over a 24h period.

Experiment 1. Male Wistar rats (n=8, b. wt. 380 - 450g) were deprived of food for 5h per day and trained to press a lever in an operant conditioning chamber on a fixed ratio 5 (FR-5) schedule for 45 mg food pellets, (Ebenezer, 1992). During experimental trials, the rats were injected i.p. with either vehicle or leptin (10 µg kg^-1) and placed in the conditioning chamber immediately after injection. Water was available ad libitum. Food intake was recorded in 5 min bins for 30 min. Each rat received both treatments in a cross over fashion; 3 days separated successive trials. The cumulative data was analysed by the paired t-test. Experiment 2. Male Wistar rats (n=8; b wt. 330 - 360g) were housed in groups of 4 with free access to food and water ( lights on at 9.00h and lights off at 21.00h). During experimental trials, the rats were injected i.p. with either saline or leptin (10 or 25 µg kg^-1) at the start of the light cycle and placed singly in separate experimental cages with free access to food and water, as described previously (Ebenezer, 1990). Cumulative food intake was measured in 30 min time bins over the 24h test period. Each rat receiving all treatments; 3 days separated successive trials. The data was analysed by ANOVA with repeated measures.

The results from Experiment 1 are illustrated in Fig. 1 and show that the hypophagic effect of leptin is apparent at short (5h) as well as longer periods (21 - 22h) of food deprivation. Analysis of the data from Experiment 2 revealed that leptin (10 and 25 µg kg^-1) had no significant effects on cumulative food intake in non-deprived rats at any of the intervals over the 24h measurement period. For example, mean cumulative intake (g) ± s.e. mean at 24h was 26.4 ± 3.1 (vehicle), 29.9 ± 1.0 (leptin 10 µg kg^-1) and 29.5 ± 1.2 (leptin 25 µg kg^-1). This is in contrast to the slow-onset but long lasting hypophagic effects (from 6 - 24h) observed in rodents following s.c. injection of sub-milligram to milligram doses of leptin, which is elicited by a central effect of the hormone (see Luheshi et al., 1999). These findings suggest that while i.p. administration of low microgram doses of leptin produces a brief (15 - 30 min;) but not long lasting (6 - 24h) hypophagia, and lends support to the view that leptin may play a role as a short-term peripheral satiety factor (Patel et al., 2003).

Fig.1. Effects of leptin on operant food intake in 5h fasted rats.

Ebenezer, I.S. (1990) NeuroReport, 1, 73 - 76.
Luheshi, G.N. et al. (1999) Proc. Natl. Acad. Sci. (USA), 96, 7047 - 7052.
Patel, J.D. et al. (2003) Br. J. Pharmacol. P. in press.
Patel, J.D. et al. (2002) Br. J. Pharmacol., 134, 118P.
Ebenezer, I.S. (1992) NeuroReport, 3, 1019 - 1022.