Differential sensitivity of c-Fos expression in hippocampus and other brain regions to moderate and low doses of alcohol

Alcohol consumption in humans is characterized by a wide range of behavioral effects and pathological consequences that suggest several neuroanatomical targets for this drug. To identify these targets we have mapped alcohol-induced changes in the expression of the c-Fos protein in the rat brain. Administration of a moderate dose of alcohol (1.5 g kg(-1)) led to a suppression of basal and novel environment-induced c-Fos expression in the hippocampus and simultaneous induction of this protein in regions important for the reinforcing as well as aversive properties of drugs. These include the extended amygdala (including the central nucleus of amygdala, bed nucleus of stria terminalis and nucleus accumbens), regions processing sensory information (including the Edinger-Westphal nucleus and the paraventricular nucleus of the thalamus) and in stress-related areas (including the paraventricular nucleus of the hypothalamus, nucleus of the solitary tract and several neocortical areas). Repeated administration of the same dose of alcohol did not decrease alcohol-mediated suppression of c-Fos in the hippocampus, but decreased alcohol-induced expression of c-Fos in other areas. A lower dose of acute alcohol (0.5 g kg(-1)) reduced basal c-Fos expression in several areas of the neocortex, hippocampus and hypothalamus. However, while this low dose of alcohol was unable to counteract the environmental novelty-induced c-Fos expression in these areas, it increased c-Fos expression in the central nucleus of amygdala (an effect similar to the one observed previously for diazepam). Our data suggest that the effects of low doses of alcohol may be due to selective GABA-like effects of ethanol, whereas higher doses of ethanol involve effects on multiple neurotransmitter systems.