REGULATION OF SEROTONIN RELEASE IN THE FRONTAL-CORTEX AND VENTRAL HIPPOCAMPUS OF HOMOZYGOUS MICE LACKING 5-HT1B RECEPTORS - IN-VIVO MICRODIALYSIS STUDIES

To assess the involvement of the serotonin receptor subtype 5-HT1B as terminal autoreceptor regulating 5-HT release in mice, we compared bas al values and potassium-evoked changes of extracellular 5-HT levels ob tained by in vivo microdialysis in two serotoninergic terminal project ion areas of conscious wild-type mice with those measured in homozygou s mutant mice lacking the gene encoding the 5-HT1B receptor. In the fr ontal cortex and ventral hippocampus, basal and K+-evoked 5-HT release did not differ between the two strains of mice studied. The infusion via reverse microdialysis of the selective 5-HT1B receptor agonist CP- 93,129 (500 nM) decreased significantly K+-evoked 5-HT release in the frontal cortex (by -44%) and ventral hippocampus (by -32%) of wild-typ e mice but had no effect in mutants. In a similar manner, the mixed 5- HT1B-5-HT1D receptor agonist sumatriptan (800 nM) decreased significan tly K+-evoked 5-HT release in the frontal cortex (by -46%) of wild-typ e mice but had no effect in mutants. These results demonstrated that 5 -HT1B knockout mice are not as sensitive to full (CP-93,129) and mixed (sumatriptan) 5-HT1B receptor agonists as are wild-type mice. These d ata provide in vivo evidence that, in mice, 5-HT1B, but not 5-HT1D, au toreceptors inhibit 5-HT release at nerve terminals located in the fro ntal cortex and ventral hippocampus.