Intraventricular insulin and leptin decrease sucrose self-administration in rats

Data from our laboratory and others have demonstrated an effect of the candidate adiposity signals insulin and leptin to decrease brain reward function, as assessed by lateral hypothalamic self-stimulation and food-conditioned place preference. In this study, we evaluated the effect of centrally administrated insulin or leptin to acutely decrease motivated performance for 5% sucrose, i.e., progressive ratio (PR) sucrose self-administration. Consistent with findings using other behavioral assays, both insulin and leptin significantly decreased the number of bar presses (62 +/- 7 and 76 +/- 8% of paired controls respectively), and the number of sucrose rewards obtained (87 +/- 4 and 91 +/- 4% of paired controls respectively), relative to within-subjects' control day performance on PR sucrose self-administration, whereas acute intraventricular cerebrospinal fluid had no effect. Rats fed a higher fat diet for 5 weeks were resistant to the effects of the intraventricular insulin or leptin, suggesting a central resistance to their action. Thus the findings of this study extend and support previous observations which suggest that neuroendocrine signals which regulate energy homeostasis in the CNS may also play a role in modulating reward circuitry, and specifically, food reward. (c) 2006 Elsevier Inc. All rights reserved.