Intracerebroventricular infusion of leptin decreases serotonin transporter binding sites in the frontal cortex of the rat.

We demonstrate that chronic intracerebroventricular infusion of leptin dramatically decreases the number of [(3)H]paroxetine binding sites in the frontal 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 treatment significantly decreases food intake, [(3)H]paroxetine binding parameters were also estimated in the frontal cortex of pair-fed control rats. No significant difference in [(3)H]paroxetine binding was observed between pair-fed and ad libitum fed control rats. These data indicate that leptin treatment could regionally down-regulate serotonin transporter binding sites in the brain. Although the cellular and molecular mechanisms underlying such an effect of leptin need further investigation, our observations support the notion of a possible interaction between leptin and the serotonergic system of potential interest in the pathophysiology of depression.