The effects of selective serotonin reuptake inhibitors on extracellular 5-HT in the hippo- campus of 5-HT1B receptor knockout mice

The effects of two selective serotonin reuptake inhibitors (SSRIs) on 5-hydroxytryptamine (5-HT) in the hippocampus were studied in wildtype and in 5-HT1B receptor knockout (KO) mice using in vivo microdialysis. Basal 5-HT levels were not different between the two genotypes. The functional absence of 5-HT1B receptors was examined in the knockout mice by local infusion of the 5-HT1B receptor agonist, CP93129 (1,4-Dihydro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-5Hpyrrolo[3,2-b]pyridin-5-one) into the hippocampus. CP93129 (1 μM) decreased 5HT levels in wildtype mice, but not in 5-HT1B KO mice. Systemic administration of the SSRI paroxetine (5 mg/kg i.p.) increased extracellular 5-HT levels. The increase of 5-HT in 5-HT1B KO mice was almost twofold higher than in wildtype mice. Systemic administration of SSRIs stimulates both terminal 5-HT1B autoreceptors and somatodendritic 5-HT1A autoreceptors. Therefore, another