Regulation of serotonin release in the frontal cortex and ventral hippocampus of homozygous mice lacking 5-HT(1B) receptors: In vivo microdialysis studies

Abstract

To assess the involvement of the serotonin receptor subtype 5-HT(1B) as terminal autoreceptor regulating 5-HT release in mice, we compared basal values and potassium-evoked changes of extracellular 5-HT levels obtained by in vivo microdialysis in two serotoninergic terminal projection areas of conscious wild-type mice with those measured in homozygous mutant mice lacking the gene encoding the 5-HT(1B) receptor. In the frontal 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-HT(1B) 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-type mice but had no effect in mutants. In a similar manner, the mixed 5-HT(1B)-5-HT(1D) receptor agonist sumatriptan (800 nM) decreased significantly K+-evoked 5-HT release in the frontal cortex (by -46%) of wild-type mice but had no effect in mutants. These results demonstrated that 5-HT(1B) knockout mice are not as sensitive to full (CP-93,129) and mixed (sumatriptan) 5-HT(1B) receptor agonists as are wild- type mice. These data provide in vive evidence that, in mice, 5-HT(1B), but not 5-HT(1D), autoreceptors inhibit 5-HT release at nerve terminals located in the frontal cortex and, ventral hippocampus.