Organic cation transporters (OCTs) are carrier-type polyspecific permeases known 
to participate in low-affinity extraneuronal catecholamine uptake in peripheral 
tissues. OCT3 is the OCT subtype most represented in the brain, yet its 
implication in central aminergic neurotransmission in vivo had not been directly 
demonstrated. In a detailed immunohistochemistry study, we show that OCT3 is 
expressed in aminergic pathways in the mouse brain, particularly in dopaminergic 
neurons of the substantia nigra compacta, non-aminergic neurons of the ventral 
tegmental area, substantia nigra reticulata (SNr), locus coeruleus, hippocampus 
and cortex. Although OCT3 was found mainly in neurons, it was also occasionally 
detected in astrocytes in the SNr, hippocampus and several hypothalamic nuclei. 
In agreement with this distribution, OCT3/Slc22a3-deficient mice show evidence 
of altered monoamine neurotransmission in the brain, with decreased 
intracellular content and increased turnover of aminergic transmitters. The 
behavioral characterization of these mutants reveal subtle behavioral 
alterations such as increased sensitivity to psychostimulants and increased 
levels of anxiety and stress. Altogether our data support a role of OCT3 in the 
homeostatic regulation of aminergic neurotransmission in the brain.