The differential effects of food restriction on 5-HT1A and 5-HT1B receptor mediated control of serotonergic transmission in the hippocampus and hypothalamus of rats

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-HT_1A autoreceptors in the raphe nuclei, and the nerve terminal 5-HT_1B autoreceptors which together regulate the synthesis and release of 5-HT in these regions. Sensitivity of the somatodendritic 5-HT_1A autoreceptors was assessed by measuring the reduction in extracellular 5-HT induced by systemic administration of the 5-HT_1A receptor agonist 8-hydroxy-2-di-n-(propylamino)-tetralin (8-OH-DPAT), while sensitivity of nerve terminal 5-HT_1B autoreceptors was measured by observing the increase in 5-HT release after systemic injection of the 5-HT_1B 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-HT_1B receptors regulate 5-HT release by a negative feedback mechanism, the decrease in sensitivity of 5-HT_1B 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.