Absence of formation of brain salsolinol in ethanol-dependent mice

The in vivo biosynthesis of tetrahydroisoquinoline (TIQ) alkaloids has been shown to occur during acute and chronic ethanol administration under experimental conditions which increase aldehyde precursors and reduce TIQ metabolism. The TIQs have been postulated to mediate some of the effects of ethanol, although their occurrence under conditions of physical dependence has not been reported. The purpose of this investigation was to determine whether in vivo TIQ formation would occur in brains of ethanol-dependent animals in the absence of specific experimental manipulations, and their role, if any, in the development of physical dependence. Mice were subjected to ethanol vapors for 6 days (14 mg/1 in inspired air on day 1, increasing to 20-30 mg/l on day 6), and were then either evaluated for withdrawal convulsions on handling or sacrificed and their brains analyzed for salsolinol (the acetaldehyde-dopamine TIQ) by gas chromatography/electron capture (assay sensitivity: 8 ng/g of tissue). No evidence could be obtained for in vivo formation of salsolinol in individual whole brains, pooled whole brains or dopamine-rich areas of pooled brains obtained from ethanol-dependent mice even under conditions where blood ethanol levels reached 7 mg/ml. In view of the low pharmacological potency of salsolinol, it is unlikely that this alkaloid plays a significant role in the effects of ethanol in mice.