A inibição do proteassoma hipocampal prejudica a reconsolidação da memória de extinção

Abstract

Extinction memory represents a new learning process that suppresses previously consolidated fear responses, and its long-term maintenance is essential for behavioral adaptation and relevant to the treatment of disorders such as post-traumatic stress disorder. Evidence indicates that the hippocampus plays a central role in memory reconsolidation processes, which depend on protein synthesis and possibly on protein degradation mediated by the ubiquitin-proteasome system (UPS). In this context, the present study investigated the role of proteasome activity in the CA1 region of the dorsal hippocampus in the persistence of extinction memory following its reactivation in male and female Wistar rats. Animals underwent an extinction protocol in the inhibitory avoidance task consisting of one daily session for five consecutive days. Extinction memory was reactivated one day after the last extinction session, and memory retention was assessed either 1 or 7 days later. The results showed that proteasome inhibition by either lactacystin (32 ng/ µl side) or MG-132 (150 ng/ µl side) induced the return of the fear response at both retention tests, indicating an impairment of extinction memory reconsolidation. This effect was also observed in females, suggesting that the underlying mechanism is conserved across sexes. Assessment of locomotor and exploratory parameters confirmed that the observed effects were not due to nonspecific pharmacological actions. Taken together, these findings demonstrate that hippocampal proteasome activity is required for the restabilization of extinction memory following its reactivation, identifying protein degradation as a critical mechanism of reconsolidation and a potential target for pharmacological interventions combined with extinction-based therapies.