In the present study, water-drinking rats exposed to ELS tendentially displayed the highest corticosterone levels [30], which is in line with the long-term impact of maternal separation and the hyporesponsivity of the HPA axis seen in rats exposed to high dam-pup interactions during early postnatal life [23]. Glucocorticoids released as a result of stress have been associated with neuroadaptations in the VTA through direct activation of GR [41], thus supporting a role of FKBP5. Persistent higher corticosterone levels follow prolonged MS in animal models of ELS [42] and are associated with decreased dopaminergic output in the Acb [43]. Since FKBP5 is a negative regulator of GR, the tendentially higher Fkbp5 expression observed here in the Acb of water-drinking rats exposed to ELS might be part of a mechanism balancing their higher corticosterone levels. On the other hand, alcohol appeared to reverse these effects. Alcohol-drinking rats exposed to ELS compared to controls displayed lower Fkbp5 expression in the Acb but higher Fkbp5 expression in the VTA. Additionally, these rats had lower corticosterone levels [30], in line with the dampening of the stress response by alcohol observed in individuals at risk to develop alcohol use disorder [21].
