AMPT partially reverses euphoric but not psychomotor effects of alcohol in humans

There are two dopaminergic brain systems that may be involved in the action of alcohol—the mesolimbic dopamine (DA) system, presumably by mediating alcohol-induced euphoria, and the mesostriatal DA system, by acting as a tonic regulatory system. In a double-blind placebo-controlled experiment, either 1,750 mg of alpha-methyl-para-tyrosine (AMPT; an inhibitor of tyrosine hydroxylase), 0.65 g/kg of alcohol, both substances combined, or a placebo only were applied to 60 healthy male subjects. Pretreatment with AMPT resulted in a pronounced reduction of urinary levels of DA, DOPAC, and HVA and caused a marked reduction in alcohol-induced euphoria, as indicated by self-ratings of joyfulness. Alcohol caused a decrease in experienced feelings of alertness and concentration as well as in critical-flicker-fusion (CFF) threshold values. In addition, lift-off time, representing a subcomponent of reaction time, was increased by alcohol, but was unaffected by AMPT. This pattern of results supports the notion of two distinct dopaminergic brain systems mediating behavioral effects of alcohol and, further, is in agreement with the hypothesis of differential sensitivity of dopaminergic and GABAergic mechanisms underlying the biphasic action of alcohol.