Leptin decreases feeding and exploratory behaviour via interactions with CCK(1) receptors in the rat.

We assessed the effects of peripheral leptin on anxiety and exploratory behaviour in the elevated plus-maze and in the four-hole box or Y-maze tests, in rats fed 80% of normal daily food intake and rats fed ad libitum. In the Y-maze test, i.p. injection of 0.4 or 1 mg/kg leptin into rationed rats significantly decreased the percentage of spontaneous alternation behaviour and increased the number of visits. In the elevated plus-maze test, rationed rats spent significantly more time in the open arms (aversive part of the maze) than did rats fed ad libitum. This difference in behaviour was abolished by injecting 0.4 mg/kg leptin. In the four-hole box test, i.p. administration of 1 mg/kg leptin significantly reduced the duration and number of hole visits in rationed and ad libitum fed rats. As with leptin inhibition of food intake, these behavioural changes caused by leptin were prevented by a CCK(1) receptor antagonist (L364,718), at a dose that had no effect by itself. Finally, a 20-min stress that increased corticosterone and ACTH levels had no effect on circulating leptin levels and on the leptin content of epididymal fat tissue, stomach and brain. Thus, leptin induces hypoexploration and decreases spontaneous alternation in rats and these effects are partly dependent on nutritional status. These results also suggest that the CCK system may be involved in the induction of these behavioural changes in rats by leptin, via the CCK(1) receptor.