Stress-induced Resistance to Fear Memory Destabilization is Associated with an Impairment of Lys-48-linked Protein Polyubiquitination in the Basolateral Amygdala: Influence of D-cycloserine

The destabilization/reconsolidation process can be triggered by memory recall, allowing consolidated memories to be modified. We have previously reported that stress prior to fear conditioning induces memories that exhibit resistance to the engagement of some molecular events associated with the destabilization/reconsolidation process. Here, we evaluated whether stress could affect the expression of Lys-48 polyubiquitinated proteins within the basolateral amygdala complex, a phenomenon crucially linked to memory destabilization. As expected, a post-recall increase of Lys-48 polyubiquitinated proteins in control animals was observed; however, this phenomenon was prevented by stress exposure before fear conditioning. On the other hand, pre-recall administration of D-cycloserine -a positive modulator of NMDA sites capable of reverting memory resistance to pharmacological interference-, facilitated the increase of Lys-48 polyubiquitinated proteins in stressed animals. In conclusion, the protein polyubiquitination-dependent destabilization is impaired after the recall of stress-induced resistant memories, with D-cycloserine restoring such molecular event. Hence, the present report contributes to further characterize the neurobiological events associated with stress-induced memory resistance as well as to corroborate the connection between glutamatergic signaling, protein degradation and memory destabilization in stress-induced resistant memories.