Dopamine Metabolism Trafficking in Genetically Defined Anxiety and Neuropathology

Abstract

As is known, brain dopamine is metabolised by the enzymes monoamine oxydase and catechol-O-methyl transferase into the final metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The very existence of two main pathways of this process gives rise to some important and so far untackled questions: what is the reason of there being two, in what way are they related and what mechanisms underlie the trafficking? In earlier studies on 8 inbred mouse strains, we established that there was a negative genotypic correlation between brain levels of DOPAC and HVA (1). At the same time, we demonstrated that while the level of either metabolite undergoes genetically defined changes, the others may remain unchanged. Rats selected for lack of aggressiveness, displayed a lower level of HVA in nucleus accumbens (2), while those selected for predisposition to catalepsy displayed a higher one (3), levels of DOPAC in both staying unchanged. These data on selective changes in HVA level in n. accumbens imply that the idea that both ways of dopamine metabolism are open at a time or that they are reciprocal, should be replaced by the hypothesis of a more or less independent functioning of either.