We continued to evaluate possible contribution of ethanol on dopamine (DA) metabolism using the LC/ESI-MS/MS method that has been developed in our laboratory. DA is metabolized by monoamine oxidase (MAO) to 3,4-dihydroxyphenylacetaldehyde (dopaldehyde, DOPAL) which is a substrate for aldehyde dehydrogenase-2 (ALDH2). Tetrahydropapaveroline (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.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2012
Total Cost
$85,516
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
Zip Code
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