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These data confirm previous observations showing selective effects of alcohol administration on immediate early gene expression. Furthermore, the effects of voluntary alcohol self-administration on immediate early gene expression differ from involuntary alcohol exposure and suggest several brain regions as substrates for alcohol consumption.

To identify alcohol-responsive brain areas, we have immunohistochemically analyzed expression of c-Fos, FosB, and other Fos-related antigens in the brain of inbred DBA/2J mice after a single or repeated injection of alcohol (4 g/kg). We observed increased expression of c-Fos after alcohol administration in the central nucleus of amygdala, paraventricular nuclei of hypothalamus and thalamus, and several other brain areas. Although increased expression of c-Fos in the nucleus accumbens was also observed, this increase was not statistically significant. Repeated administration of alcohol had the tendency to reduce alcohol-induced c-Fos expression in these areas. Immunohistochemical analysis using an antibody recognizing most Fos-related antigens revealed increases of expression of these proteins in a partially overlapping set of brain regions. In contrast to c-Fos, FosB expression was found to be elevated significantly higher after repeated than after acute treatment with alcohol in several brain areas, including the shell of nucleus accumbens. In contrast to previous c-Fos studies, our studies confirm that alcohol administration indeed activates the reward circuits, including the basal ganglia, and suggest that FosB could serve as a more sensitive marker for this activation.