Expression of cFos and brain-derived neurotrophic factor in cortex and hippocampus of ethanol-withdrawn male and female rats

Objective: To map areas of brain activation (cFos) alongside changes in levels of brain-derived neurotrophic factor (BDNF) to provide insights into neuronal mechanisms contributing to previously observed sex differences in behavioral measures of ethanol withdrawal (EW). Materials and Methods: Immunohistochemical analysis of cFos and BDNF levels using protein-specific antibodies and visualization with nickel-enhanced DAB staining in 3 cortical and 4 hippocampal regions was used to assess EW-induced expression of these proteins. Results: EW male and female rats showed significantly higher levels of cFos expression compared to controls in the hippocampal regions whereas EW OVX rats showed higher levels compared to controls only at 1 day EW in the dentate gyrus. Males expressed higher basal levels of cFos in the CA1 subfield of the hippocampus and in the motor cortex than either intact or OVX female rats. BDNF immunoreactivity was also significantly higher in EW rats compared to that in controls, varying with sex and brain region at 1 and 3 days EW. Conclusions: Sex-and brain region-specific changes in expression of cFos and BDNF occurring during 1 and 3-day EW, suggest that differential activation and expression of neurotrophins may influence the observed sex differences and support the suggestion that EW is a chronic stressor, eliciting sequential neuronal activation and neurotrophin regulation.