Pharmacological Blockade of GABA-A receptors in the Basolateral Amygdala Complex Prevented the Disrupting Effect Of Midazolam on Fear Memory Reconsolidation. Influence of D-Cycloserine

Congreso; XXX Reunión anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Consolidated memories can enter into a labile state after retrieval, requiring arestabilization process defined as reconsolidation. This process can be interfered by agents such as protein synthesis inhibitors or benzodiacepines. However, there are conditions that constraint the occurrence of labilization/reconsolidation process. For instance, memory age, strength of training among others. Previous studies shown that stress prior to contextual fear conditioning generates a memory resistant to the disrupting effect of Midazolam (MDZ) on reconsolidation. Furthermore, it is known that stress leads to reduced GABAergic transmission in Basolateral Amygdala (BLA), promoting LTP and fear memory formation. Interestingly, these effects are mimicked by intra-BLA administration of Bicuculine (BIC), a GABA-A receptor antagonist. Therefore, this study was aimed to evaluate if BIC intra-BLA prior to fear conditioning generates resistance to the effect of MDZ in a similar way to the resistance generated by stress. As expected, infusion of BIC mimics the effect of stress in generating a memory insensitive to MDZ interference. Additionally, this resistance is reverted by systemic administration of D-Cycloserine, an NMDA receptor co-agonist, prior to memory reactivation. These results demonstrates that BLA hyperexcitability leads to the formation of resistant memories, and that the onset of the labilization phase can be promoted by activation of NMDA receptor at the moment of retrieval.