Modulation of neuropeptide Y overflow by leptin in the rat hypothalamus, cerebral cortex and medulla

This study examined whether leptin can exert inhibitory actions on brain NPY overflow in Sprague-Dawley and in lean and obese Zucker rats, and tested the site-specificity of the effect. Slices of rat hypothalamus, cerebral cortex and medulla oblongata were perfused with modified Krebs buffer containing either leptin or KCl. Depolarization of tissues with 40 mM KCl elicited a significant doubling of NPY overflow in all brain regions tested. At 1 microM, leptin significantly reduced NPY overflow only in the rat hypothalamus, while at 3 microM, leptin reduced NPY overflow from all regions. However, no effect of 1 microM leptin was observed in the hypothalamus of obese Zucker rats: this insensitivity to leptin is in keeping with their genetic defect. In conclusion, the inhibitory effect of leptin on hypothalamic NPY overflow provides further evidence for important modulatory actions between these two feeding mediators. Moreover, the effect of leptin observed in the cerebral cortex and medulla oblongata supports a role of leptin in brain regions other than the hypothalamus.