Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice.
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.
Inserm U513, Université Paris VI, Paris, France, and UPMC, Université Paris VI, Paris, France.
Vincent
V
Vialou
Laure
L
Balasse
Jacques
J
Callebert
Jean-Marie
JM
Launay
Bruno
B
Giros
Sophie
S
Gautron
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D006706:Homeostasis / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D027701:Organic Cation Transport Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics* / Q000502:physiology; D000099254:Organic Cation Transporter 3
D015306:Biogenic Monoamines; D027701:Organic Cation Transport Proteins; D000099254:Organic Cation Transporter 3