Pharmacopsychiatry 2003; 36 - 192
DOI: 10.1055/s-2003-825443

An organic cation transporter capable of transporting serotonin is upregulated in serotonin transporter-deficient mice

R Mössner 1, A Schmitt 1
  • 1Department of Psychiatry and Psychotherapy, University of Würzburg, Würzburg, Germany

The serotonin (5HT) transporter (5HTT) regulates serotonergic neurotransmission by mediating the reuptake of 5HT from the synaptic cleft. The organic cation transporter (OCT) gene family physiologically transports a wide spectrum of organic cations. Although lacking the high affinity and selectivity of the 5HTT, OCT1 and OCT3 mediate low-affinity 5HT transport and therefore may participate in the clearance of excessive 5HT. Since concentrations of extracellular 5HT are increased in the brain of 5HTT-deficient mice, we investigated the role of OCTs in 5HT system homeostasis. We analyzed OCT1 and OCT3 gene expression in the brain of 5HTT knockout mice by semi-quantitative competitive PCR and in situ hybridization. We demonstrate that in 5HTT-deficient mice OCT3 mRNA concentrations were significantly increased in the hippocampus. In contrast, OCT1 expression was unchanged. Upregulation of OCT3 expression and enhanced low-affinity 5HT uptake may limit the adverse effects of elevated extracellular 5HT and may play a critical role in maintaining 5HT-dependent functions of the hippocampus in the absence of 5HTT.