Acute ethanol induces Fos in GABAergic and non-GABAergic forebrain neurons: a double-labeling study in the medial prefrontal cortex and extended amygdala

The purpose of this study was to further address the hypothesis that ethanol activates GABAergic neurons in specific brain neurocircuits that mediate motivated behavior and control of action, such as the central extended amygdala and medial prefrontal cortex. Male Sprague-Dawley rats received habituation to 7 days of daily intragastric administration of water (5 ml/kg) followed by a single acute intragastric dose of ethanol (2.5 g/kg) or water then, 2 h later, by paraformaldehyde perfusion. Rats left undisturbed in the animal room throughout the experiment were also perfused (naive group). Brain sections were processed for single Fos immunohistochemistry or dual Fos immunohistochemistry/glutamic acid decarboxylase (GAD) mRNA in situ hybridization. Intragastric water administration increased the number of Fos-immunoreactive cells in the infralimbic cortex and lateral part of the central nucleus of the amygdala compared with the naive group. Ethanol administration increased the number of Fos-immunoreactive cells in the infralimbic (+57.5%) and prelimbic (+105.3%) cortices, nucleus accumbens shell region (+88.2%), medial part of the central nucleus of the amygdala (+160%), and lateral part of the bed nucleus of the stria terminalis (+198.8%) compared with the water-treated group. In the nucleus accumbens shell region, central nucleus of the amygdala, and bed nucleus of the stria terminalis, more than 80% of Fos-immunoreactive neurons were GABAergic after ethanol administration. In contrast, in the prelimbic cortex, 75% of Fos-immunoreactive neurons were not GABAergic. These results constitute new evidence for region-specific functional interactions between ethanol and GABAergic neurons.