It is known that under certain boundary conditions, the retrieval of a stable consolidated memory results into a labile one followed by a stabilization period termed reconsolidation. During the instability phase, memory trace can be disrupted by a number of pharmacological agents. In the current research, adult male rats were conditioned in a contextual fear paradigm; the consolidated fear memory was reactivated by the re-exposure to the associated context for different periods of time that were followed by midazolam (MDZ) administration. In the first set of experiments, we study the effectiveness of different MDZ doses in preventing reconsolidation of different memory ages. Memory reconsolidation was disrupted when the reactivation lasted 3-5 min. Over a 10 min reactivation session, all rats gradually reduce their fear response, which indicates the emergence of an extinction period. Following this period, MDZ blocked the consolidation of extinction. In a brief reactivation session, MDZ (1-1.5 mg/Kg) attenuated the reconsolidation of recent memories. Remote memories were only disrupted with higher MDZ doses (3 mg/Kg) regardless of the reactivation trial´s duration. An additional goal of the present study was to evaluate the vulnerability of recent and remote memories in animals that have experienced a stressful situation. The results show that MDZ did not affect memory reconsolidation in older-than-one-day memories of stressed animals, not even after the administration of higher MDZ doses and a longer reactivation session. We investigated whether activating NMDA sites prior to reactivation by D-cycloserine (DCS), a partial NMDA agonist, promotes the destabilization of resistant memories such as those of stressed rats. Our findings indicate that DCS prior to reactivation promotes retrieval-induced lability in a resistant memory trace since MDZ-induced memory impairment in stressed animals became evident with pre-reactivation DCS but not after pre-reactivaction vehicle. In sum, MDZ could be potentially used as a pharmacological intervention to interfere with traumatic memories. The combined treatment with DCS favours the effectiveness of MDZ´s disruptive effect on fear memory reconsolidation.
