Enhancing a declarative memory in humans: the effect of clonazepam on reconsolidation

Abstract

A consolidated memory recalled by a specific reminder can become unstable (labile) and susceptible to facilitation or impairment for a discrete period of time. This labilization phase is followed by a process of stabilization called reconsolidation. The phenomenon has been shown in diverse types of memory, and different pharmacological agents have been used to disclose its presence. Several studies have revealed the relevance of the GABAergic system to this process. Consequently, our hypothesis is that the system is involved in the reconsolidation of declarative memory in humans. Thus, using our verbal learning task, we analyzed the effect of benzodiazepines on the re-stabilization of the declarative memory. On Day 1, volunteers learned an association between five cue- response-syllables. On Day 2, the verbal memory was labilized by a reminder presentation, and then a placebo capsule or 0.25 mg or 0.03 mg of clonazepam was administered to the subjects. The verbal memory was evaluated on Day 3. The volunteers who had received the 0.25 mg clonazepam along with the specific reminder on Day 2, exhibited memory improvement. In contrast, there was no effect when the drug was given without retrieval, when the memory was simply retrieved instead of being reactivated or when short-term memory testing was performed 4 h after reactivation. We discuss the GABAergic role in reconsolidation, which shows a collateral effect on other memories when the treatment is aimed at treating anxiety disorders. Further studies might elucidate the role of GABA in the reconsolidation process associated with dissimilar scenarios.