Serotonergic pathways are considered important in the regulation of appetite. We have determined, in female rats, the effects of 4 weeks food restriction (FR) on serotonin function, using in vivo microdialysis. We recorded basal 5-HT release in the hypothalamus and hippocampus, and the sensitivity of the somatodendritic 5-HT1A autoreceptors in the raphe nuclei, and the nerve terminal 5-HT1B autoreceptors which together regulate the synthesis and release of 5-HT in these regions. Sensitivity of the somatodendritic 5-HT1A autoreceptors was assessed by measuring the reduction in extracellular 5-HT induced by systemic administration of the 5-HT1A receptor agonist 8-hydroxy-2-di-n-(propylamino)-tetralin (8-OH-DPAT), while sensitivity of nerve terminal 5-HT1B autoreceptors was measured by observing the increase in 5-HT release after systemic injection of the 5-HT1B receptor antagonist GR 127935. Basal release of 5-HT was not affected by FR. 8-OH-DPAT decreased 5-HT release in the hippocampus and hypothalamus in both groups, while GR 127935 increased 5-HT release in both areas in the control animals but not in the hypothalamus of the FR animals. Since 5-HT1B receptors regulate 5-HT release by a negative feedback mechanism, the decrease in sensitivity of 5-HT1B receptors in the hypothalamus of FR rats indicates increased serotonergic transmission in these rats. The fact that such differential effects on 5-HT release appeared only in the hypothalamus, the center of regulation of energy balance, suggests a compensatory role in FR by increasing 5-HT secretion, thereby reducing feeding behavior.