Leptin reverses sucrose-conditioned place preference in food-restricted rats

Previous studies have suggested that food restriction can modify performanc e in the conditioned place preference (CPP) paradigm. In the present study, we tested the hypotheses that food restriction would enhance the developme nt of a CPP to low-calorie sucrose pellets and that peripheral leptin repla cement in food-restricted animals would reverse this effect. Using a range of 45-mg sucrose pellets (0-15 pellets) as a reward, we observed that a sig nificant place preference was conditioned in food-restricted, but not ad li bitum-fed rats. This CPP was reversed either by treatment of food-restricte d rats with the dopamine receptor antagonist ol-flupenthixol (200 mug/kg ip ) during the training protocol or by chronic subcutaneous replacement of le ptin (125 mug/kg/day) that attenuated the food restriction-induced decrease of circulating leptin. We conclude that dopaminergic signaling and the fal l of plasma leptin concentrations contribute to the CPP of food-restricted rats. This finding suggests that in addition to metabolic adaptations, hypo leptinemia results in behavioral adaptations during states of energy depriv ation. (C) 2001 Elsevier Science Inc. All rights reserved.