Interactions between serotonin and dopamine in the striatum are not mediated by striatal 5-HT1B receptors

In vivo microdialysis was performed in wildtype and 5-HT1B receptor knockout mice to explore the role of 5-HT1B receptors in striatal serotonin (5-HT) and dopamine (DA) outflow. Local administration of the selective 5-HT reuptake inhibitor fluvoxamine (0.1 – 10 μM) dose-dependently increased 5-HT to the same extent in wildtype and 5-HT1B receptor knockout mice. The 5-HT1B receptor agonist CP93129 (0.5 μM) reduced 5-HT levels wildtype mice, but did not affect DA outflow. Striatal DA outflow was increased 5-fold by 50 μM CP93129, in wildtypes and surprisingly, 5-HT1B receptor knockout mice showed an identical response. The CP93129-induced DA increase was not attenuated by ritanserin, a 5-HT2A/2C receptor antagonist, but was completely blocked by tetrodotoxin, demonstrating that the DA release was from a neuronal origin. Increased striatal 5-HT levels should indirectly activate 5-HT receptors that facilitate DA release. The 5-HT releaser fenfluramine (50 μM) and the SSRI fluvoxamine (10 μM) both increased 5-HT and DA levels, but their effect was not different between the genotypes. Concluding, striatal 5-HT1B autoreceptors are functionally present, but do not play a significant role in the effects of SSRIs on extracellular 5-HT. The results in 5HT1B knockout mice do not support a role of striatal 5-HT1B heteroreceptors in DA outflow in the striatum.