Intracerebroventricular infusion of leptin decreases serotonin transporterbinding sites in the frontal cortex of the rat

We demonstrate that chronic intracerebroventricular infusion of leptin dram atically decreases the number of [H-3]paroxetine binding sites in the front al cortex of the rat brain. In contrast, the density in paroxetine binding sites estimated in the region containing raphe projecting cell bodies (i.e. , the dorsal and median raphe nuclei) remains unchanged. Since leptin treat ment significantly decreases food intake, [H-3]paroxetine binding parameter s were also estimated in the frontal cortex of pair-fed control rats. No si gnificant difference in [H-3]paroxetine binding was observed between pair-f ed and ad libitum fed control rats. These data indicate that leptin treatme nt could regionally downregulate serotonin transporter binding sites in the brain. Although the cellular and molecular mechanisms underlying such an e ffect of leptin need further investigation, our observations support the no tion of a possible interaction between leptin and the serotonergic system o f potential interest in the pathophysiology of depression. (C) 2000 Elsevie r Science Ireland Ltd. All rights reserved.