Drug addiction may be regarded as a “disease of the brain reward system, “with dopamine implicated as the main neurotransmitter involved in the process.1 Addictive drugs “exhibit a wide range of structures and actions, but the unifying principle appears to be that they each acutely enhance striatal dopamine neurotransmission by means that dissociate it from normal drive by environmental cues.”2 Drug self-administration is done to keep nucleus accumbens dopamine within a specific elevated range so as to maintain a desired hedonic level.3

It has been proposed that the dopamine release, particularly in the nucleus accumbens, signals the salience of the stimulus to the individual and underlies the alcohol-seeking compulsion.4 Human beings vary greatly in their dopamine response to alcohol; this variation is related to genetic susceptibility for alcoholism, which contributes to more than half of alcoholism risk.5

Ethanol in alcohol provides the pharmacologic mechanism of dopamine release6—an effect that can be achieved through many forms of ethanol administration. Prior studies of oral alcohol suggest that striatal DA may be released as a function of the pharmacologic effects of alcohol.7

However, non-biochemically mediated alcohol-associated cues are also known to provoke striatal DA transmission, a phenomenon linked to the motivated behaviors associated with addiction.7 For example, alcohol-conditioned cues can independently provoke ventral striatal dopamine response in animals, which are reflective of motivated behavior and alcohol seeking.8 These cues may be separate from the biochemical mechanism of ethanol.