Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice

J Neurochem. 2008 Aug;106(3):1471-82. doi: 10.1111/j.1471-4159.2008.05506.x. Epub 2008 May 30.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biogenic Monoamines / physiology*
  • Brain / metabolism*
  • Brain / physiology
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Activity / physiology
  • Organic Cation Transport Proteins / deficiency*
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / physiology*
  • Synaptic Transmission / genetics*
  • Synaptic Transmission / physiology


  • Biogenic Monoamines
  • Organic Cation Transport Proteins
  • solute carrier family 22 (organic cation transporter), member 3