The serotonin (5HT) transporter (5HTT) regulates serotonergic neurotransmission 
by mediating the reuptake of 5HT from the synaptic cleft. Although lacking the 
high affinity and selectivity of the 5HTT, the brain expresses a large number of 
other transporters, including the polyspecific organic cation transporters 
(OCTs). OCT1 and OCT3, members of the potential-sensitive organic cation 
transporter gene family, physiologically transport a wide spectrum of organic 
cations. In addition, both transporters mediate low-affinity 5HT transport and, 
therefore, may participate in the clearance of excessive 5HT. Because 
concentrations of extracellular 5HT are increased in the brain of 5HTT-deficient 
mice, they are a model for investigating the role of OCTs in 5HT system 
homeostasis. Here, we analyzed OCT1 and OCT3 gene expression in the brain of 
5HTT knockout mice by semiquantitative competitive polymerase chain reaction and 
in situ hybridization. We demonstrate that, in 5HTT-deficient mice, OCT3 mRNA 
concentrations were significantly increased in the hippocampus, but not in other 
brain regions, including cortex, striatum, cerebellum, and brainstem. In 
contrast, no difference in OCT1 expression was detected between 5HTT knockout 
and control mice. Up-regulation 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.