ELS associates with long-term molecular changes in the mesocorticolimbic and striatal systems increasing vulnerability to addiction [13]. Herein, the effect of ELS-mediated sensitivity to alcohol drinking on Fkbp5 expression localized in the mesocorticolimbic, but not striatal, dopaminergic brain regions. An opposite effect of ELS and alcohol was observed on Fkbp5 expression in the VTA and Acb. In the VTA, rats exposed to ELS through prolonged maternal separation (MS360) had lower Fkbp5 expression than the MS15 rats. Furthermore, alcohol drinking affected Fkbp5 expression only in the MS360 rats, which displayed higher levels, towards those seen in the MS15 rats. The gene expression difference in response to voluntary drinking could contribute to the higher propensity for excessive alcohol intake that usually emerges after 3 to 5 weeks of voluntary consumption in MS360 compared to MS15 rats [14]. Interestingly, in the VTA, the direction of the interaction effect was opposite to that in the Acb, likely indicating region-dependent molecular mechanisms involving Fkbp5 in relation to ELS and alcohol in dopaminergic projecting compared to receiving areas, VTA vs. Acb.
