Novel aspects of dopamine oxidative metabolism (confounding outcomes take place of certainties)

Understanding dopamine (DA) oxidative metabolism allows to get a deeper ins ight into neurologic and psychiatric disorders featured by an altered DA ne urotransmission as well as developing appropriate therapeutic strategies. O xidative DA deamination is carried out by two highly conserved isoenzymes: monoamine oxidase (MAO) A and B; these isoenzymes both metabolize DA to dih ydroxyphenylacetaldehyde (DOPALD), which, in turn, is converted to dihydrox yphenylacetic acid (DOPAC). In the past twenty years most studies on MAO ac tivity were performed using brain dialysis in freely moving rats and measur ing DA and DOPAC levels after administration of specific MAO inhibitors. Th is led to concepts on DA metabolism grounded on a single brain area (striat um) investigated, almost exclusively, in a single animal species (rat). The se experiments were based on measurement of striatal levels of DOPAC which represents the indirect product of MAO activity. At present, the specific r ole of each MAO isoform appears to differ significantly depending on varyin g experimental conditions such as measuring the direct product of DA metabo lism. In particular, recent studies allowed the estimate of the first metab olite (DOPALD) formed by MAO, showing that DOPAC levels do not necessarily reflect MAO activity. Again, the relative contribution of the two MAO iso f orms in sustaining DA metabolism varies considerably, depending on the anim al species and the specific brain area (either striatum or substantia nigra ) under investigation. In this article we will briefly review these concept s in light of new evidence derived from innovative approaches: improved in vivo analysis of direct MAO metabolic products, measurement of oxidative me tabolism in different parts of the DA nigrostriatal pathway; measurement of MAO activity in various animal species including MAO knockout mice.