Corticosteroid-Binding Globulin Deficiency Specifically Impairs Contextual and Recognition Memory Consolidation in Male Mice

Abstract

Background/Aims: Glucocorticoids are essential in modulating memory processes of emotionally arousing experiences and we have shown that corticosteroid-binding globulin (CBG) influences glucocorticoid delivery to the brain. Here, we investigated the role of CBG in contextual and recognition long-term memory according to stress intensity. Method: We used adult male mice totally deficient in CBG (Cbg KO) or brain-specific Cbg KO (Cbg^Camk KO) to examine their performance in contextual fear conditioning (CFC) and au­ditory fear conditioning, both at short (1 h) and long-term (24 h). Long-term memory in Cbg KO was further analyzed in conditioned odor aversion and in novel object recognition task (NORT) with different paradigms, that is, with and without prior habituation to the context, with a mild or strong stressor applied during consolidation. In the NORT experiments, total and free glucocorticoid levels were measured during consolidation. Results: Impaired memory was observed in the Cbg KO but not in the Cbg^Camk KO in the CFC and the NORT without habituation when tested 24 h later. However, Cbg KO displayed normal behavior in the NORT with previous habituation and in the NORT with a mild stressor. In condition of the NORT with a strong stressor, Cbg KO retained good 24 h memory performance while controls were impaired. Total and free glucocorticoids levels were always higher in controls than in Cbg KO except in NORT with mild stressor where free glucocorticoids were equivalent to controls. Conclusions: These data indicate that circulating but not brain CBG influences contextual and recognition long-term memory in relation with glucocorticoid levels.