Leptin is an adipocyte-derived anorexic
hormone that exerts its effects via the hypothalamus and other brain regions, including the reward system.
Leptin-deficient ob/ob mice that present
morbid obesity,
hyperphagia,
insulin resistance, and
infertility are one of the most investigated mouse models of
obesity. Conditioned place preference (
CPP) paradigm is a standard behavioral model to evaluate the rewarding value of substrates. While
leptin is reported to decrease the
CPP of lean mice for high fat diet (HFD), it is unknown how
CPP toward HFD is affected by
leptin replacement in the pathophysiological condition of ob/ob mice. In the present study, we performed the
CPP test in order to clarify the effect of
leptin on the preference of ob/ob mice for HFD. Ob/ob mice had a significantly higher HFD preference in
CPP test when compared with wild-type (WT) mice and this preference was suppressed to the levels comparable to the WT mice by
leptin replacement with or without normalization of
body weight. These results demonstrate that
leptin decreases the reward value of HFD independently of
obesity, suggesting that
leptin reduces food intake by suppressing the hedonic feeding pathway in ob/ob mice.