Leptin decreases feeding and exploratory behaviour via interactions with CCK1 receptors in the rat

We assessed the effects of peripheral leptin on anxiety and exploratory beh aviour 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 si gnificantly decreased the percentage of spontaneous alternation behaviour a nd 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 abolis hed by injecting 0.4 mg/kg leptin. In the four-hole box test, i.p. administ ration of 1 mg/kg leptin significantly reduced the duration and number of h ole visits in rationed and ad libitum fed rats. As with leptin inhibition o f food intake, these behavioural changes caused by leptin were prevented by a CCK1 receptor antagonist (L364,718), at a dose that had no effect by its elf. Finally, a 20-min stress that increased corticosterone and ACTH levels had no effect on circulating leptin levels and on the leptin content of ep ididymal fat tissue, stomach and brain. Thus, leptin induces hypoexploratio n and decreases spontaneous alternation in rats and these effects art: part ly dependent on nutritional status. These results also suggest that the CCK system may be involved in the induction of these behavioural changes in ra ts by leptin, via the CCK1 receptor. (C) 2001 Elsevier Science Ltd. All rig hts reserved.