Even after 3 weeks of repeated exposure to 40 mM ethanol, a single 24 h withdrawal largely reversed the effects of ethanol. There were nearly no genes that significantly differed between the withdrawn cells and the untreated cells (Supplementary Table S1), and the comparison of CIE-treated to the withdrawn cells is very similar to the comparison of CIE-treated to control (unexposed) cells (Supplementary Figure 2). The latter pair of comparisons shows that the return to baseline is not complete, but clearly substantial. There have been several studies of the timecourse of the effects of CIE in C57BL/6J mice (exposed via vapor chamber). There were many changes in gene expression detected immediately after 4 weeks of CIE exposure, with a slight drop in differentially expressed mRNAs and a more pronounced drop in differentially expressed miRNAs 8 h later and a further drop after 120 h (Osterndorff-Kahanek et al., 2015, 2018). Those experiments provided evidence for overrepresentation of genes characteristic of astrocytes and microglia in the amygdala and to a lesser extent in the nucleus accumbens at the early times, but no
