Glucose may Contribute to Retrieval and Reconsolidation of Contextual Fear Memory Through Hippocampal Nr4a3 and Bdnf mRNA Expression and May Act Synergically with Adrenaline

Abstract

AbstractAdrenaline (Ad) and glucose released into the bloodstream during stress may strengthen contextual fear memory. However, no previous studies have detached the effects of glucose from Ad in this paradigm. Using Ad-deficient mice, we aimed to evaluate the effect of glucose on contextual fear memory when endogenous Ad is absent. Fear conditioning was performed in wild-type (WT) and Ad-deficient mice (129 × 1/SvJ) administered with glucose (30 or 10 mg/kg; i.p.) or/and Ad (0.01 mg/kg; i.p.) or vehicle (0.9% NaCl; i.p.). Catecholamines were quantified using HPLC-ED. Real-time qPCR was used to assess mRNA expression of hippocampal genes. WT and Ad-deficient mice display increased contextual fear memory when administered with glucose both in acquisition and context days when compared to vehicle. Also, Nr4a3 and Bdnf mRNA expression increased in glucose-administered Ad-deficient mice. Sub-effective doses of glucose plus Ad administered simultaneously to Ad-deficient mice increased contextual fear memory, contrary to independent sub-effective doses. Concluding, glucose may be an important part of the peripheral to central pathway involved in the retrieval and reconsolidation of fear contextual memories independently of Ad, possibly due to increased hippocampal Nr4a3 and Bdnf gene expression. Furthermore, Ad and glucose may act synergically to strengthen contextual fear memory.