Previous stress and the pharmacological blockade of GABA-A receptors in the basolateral amygdala attenuated the interfering effect of midazolam on fear memory reconsolidation.

Congreso; 9th World Congress. International Brain Research Organization (IBRO).; 2015

Learning and memory are dynamic and reconstructive processes. It is well known that a fully consolidated memory can enter into a new labile state when is retrieved, requiring an additional restabilization process defined as reconsolidation. This process can be interfered by several agents, including glutamatergic receptor antagonists, protein synthesis inhibitors or even benzodiacepines. However, not all memories enter in this retrieval-induced instability. There are known as boundary conditions that constraint theoccurrence of this labilization/restabilization process. For instance, memory age, strength of training,reminder duration, among others, determines the susceptibility of memory to enter in the mentioned process. Previous studies in our laboratory have shown that a stressful event prior to contextual fear conditioning generates a memory that is resistant to the disruptive effect of Midazolam (MDZ), a short action benzodiacepines, which interferes memory reconsolidation when is administered after retrieval in unstressed animals. On the other hand, it has been shown that stress causes an increase in the excitability of Basolateral Amygdala (BLA) by reducing GABAergic transmission, this hyperexcitability promotes LTP induction in BLA and fear memory formation. Interestingly, this effects can be mimicked by intra-BLA administration of Bicuculine (BIC), a GABA-A receptor antagonist. Therefore, the goal of this study was to evaluate if BIC intra- BLA prior to contextual fear conditioning generates resistance to the interfering effect of MDZ in a similar manner to the resistance generated by stress. As expected, rats stressed prior to fear conditioning were resistant to the disruptive effect of MDZ on memory reconsolidation, in a similar way, intra-BLA infusion of BIC prior to fear conditioning also generates a memory that remains insensitive to the interfering effect of MDZ compared with Saline (SAL) infused animals, without modification of fear memory expression at the moment of retrieval. This result demonstrates that BLA hyperexcitability caused either by stress or GABA-A antagonists leads to the formation of memories that are less susceptible to enter in labilization/reconsolidation process. Finally, we propose that the emotional state at the moment of learning is a key factor in determining the dynamic of memory.