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). During this period, we have extended our analysis to tetrahydroppapaveroline (THP), a condensation product of DOPAL and DA. We established a sensitive mass spectrometric analysis method to simultaneously determine THP, DA and SAL using the similar isolation and derivatization approaches. The recovery of THP from stripped plasma and brain tissues was greater than 80% at low pg levels. This approach allowed us to determine their levels in various regions of the rat brain. In a rat relapse model where an ALDH2 inhibitor has been shown to prevent cocaine-induced reinstatement, we found concomitant increases of THP in VTA, substantia nigra and nucleus accumbens. These data suggested that increasing THP by selective ALDH-2 inhibition may have therapeutic potential for human cocaine addiction and preventing relapse.
| 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 |
