The present address of A. Tammimaki is the Institute of Behavioral Genetics, University of Colorado at Boulder, Boulder, CO 80309, USA.
Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving mice
Article first published online: 1 JUL 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 114, Issue 6, pages 1745–1755, September 2010
How to Cite
Käenmäki, M., Tammimäki, A., Myöhänen, T., Pakarinen, K., Amberg, C., Karayiorgou, M., Gogos, J. A. and Männistö, P. T. (2010), Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving mice. Journal of Neurochemistry, 114: 1745–1755. doi: 10.1111/j.1471-4159.2010.06889.x
- Issue published online: 2 SEP 2010
- Article first published online: 1 JUL 2010
- Received March 31, 2010; revised manuscript received June 22, 2010; accepted June 22, 2010.
- prefrontal cortex;
- uptake inhibition
J. Neurochem. (2010) 114, 1745–1755.
Catechol-O-methyltransferase (COMT) plays an active role in the metabolism of dopamine (DA) in the prefrontal cortex (PFC). Because of low levels of dopamine transporter (DAT), it is proposed that the majority of released DA is taken up by either norepinephrine transporter (NET) and subsequently metabolized by monoamine oxidize (MAO) or by uptake2 (to glial cells and post-synaptic neurons) and metabolized by COMT. However, a comprehensive in vivo study of rating the mechanisms involved in DA clearance in the PFC has not been done. Here, we employ two types of microdialysis to study these pathways using DAT, NET and MAO blockers in conscious mice, with or without Comt gene disruption. In quantitative no-net-flux microdialysis, DA levels were increased by 60% in the PFC of COMT-knockout (ko) mice, but not in the striatum and nucleus accumbens. In conventional microdialysis studies, we showed that selective NET and MAO inhibition increased DA levels in the PFC of wild-type mice by two- to fourfold, an effect that was still doubled in COMT-ko mice. Inhibition of DAT had no effect on DA levels in either genotype. Therefore, we conclude that in the mouse, PFC COMT contributes about one half of the total DA clearance.