3,4-dihydroxyphenylacetic acid (DOPAC) is a metabolite of dopamine formed through deamination by monoamine oxidase (MAO).1 DOPAC is further metabolized by catechol-O-methyltransferase (COMT) to form homovanillic acid, and DOPAC levels are increased 5- to 6-fold compared to wild-type in the nucleus accumbens, striatum, and prefrontal cortex of COMT knockout mice. DOPAC oxidation is catalyzed by α-synuclein and oxidized DOPAC binds to monomeric α-synuclein preventing fibrillation.2 In vivo, foot shock stress increases DOPAC levels relative to control by approximately 45% in the prefrontal cortex and by 15% in the olfactory tubercles and ventral tegmental area (VTA) in rats.3
1.K?enmaki, M., Tammim?ki, A., My?h?nen, T., et al.Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving miceJ. Neurochem.114(6)1745-1755(2010) 2.Zhou, W., Gallagher, A., Hong, D.P., et al.At low concentrations, 3,4-dihydroxyphenylacetic acid (DOPAC) binds non-covalently to α-synuclein and prevents its fibrillationJ. Mol. Biol.388(3)597-610(2009) 3.Deutch, A.Y., Tam, S.Y., and Roth, R.H.Footshock and conditioned stress increase 3,4-dihydroxyphenylacetic acid (DOPAC) in the ventral tegmental area but not substantia nigraBrain Res.333(1)143-146(1985)