Using the LC/ESI-MS/MS method that was developed during past review periods, we continued to evaluate possible contribution of ethanol on dopamine (DA) metabolism. DA is metabolized by monoamine oxidase (MAO) to 3,4-dihydroxyphenylacetaldehyde (dopaldehyde, DOPAL) which is a substrate for aldehyde dehydrogenase-2 (ALDH2). Tetrahydroppapaveroline (THP) is a condensation product of DOPAL and DA and can be determined simultaneously along with DA and SAL using the LC/ESI-MS/MS method established previously. As the abnormal DA metabolism appears to be the target for discovering biological markers for alcoholism, we continued our efforts to develop a strategy to survey DA-metabolism using a sensitive mass spectrometric analysis method and stable-isotope labeled DA. Once candidate metabolites are identified, we will examine their levels in human alcoholics in comparison to control subjects to identify better markers for alcoholism and potential therapeutic target events in DA metabolism.

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National Institute on Alcohol Abuse and Alcoholism
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Lee, Jeongrim; Ramchandani, Vijay A; Hamazaki, Kei et al. (2010) A critical evaluation of influence of ethanol and diet on salsolinol enantiomers in humans and rats. Alcohol Clin Exp Res 34:242-50
Yao, Lina; Fan, Peidong; Arolfo, Maria et al. (2010) Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis. Nat Med 16:1024-8