Elsevier

Neuroscience

Volume 139, Issue 3, 2006, Pages 831-842
Neuroscience

Behavioural neuroscience
Midazolam disrupts fear memory reconsolidation

https://doi.org/10.1016/j.neuroscience.2005.12.064Get rights and content

Abstract

The current research examines the influence of midazolam (MDZ) on memory reconsolidation using a contextual fear paradigm in rats, based on three context-shock training trials (0.7 mA, 3 s). First, we evaluate the effect of MDZ (1 mg/kg, i.p.) injected shortly after the training procedure. Second, we examined the influence of MDZ after a brief exposure (90 s) either in the training context (reactivation procedure) or in a neutral environment (no reactivation procedure) and one day later, freezing behavior was scored when rats were re-exposed to the training environment. Third, we investigate both the effect of MDZ administered at different times following reactivation on fear memory and the persistence of such effect 10 days after reactivation. Finally, we test whether the MDZ effect could be reverted by a single weak training trial (0.2 mA, 3 s) or by the presentation of the same unconditioned stimulus in the absence of the conditioned stimulus as a reminder which proves to induce significant freezing in rats not previously trained. Results show that MDZ interferes with the formation of a contextual fear memory only when administered after the reactivation procedure but not after the training procedure. This interference was effective up to 60 min after reactivation and not at a later time. No spontaneous recovery of freezing behavior was observed 11 days after MDZ injection which was not reverted by a weak training trial and by the unconditioned stimulus alone. All these data support the idea that stimulating GABA A receptor sites via MDZ selectively disrupts the reconsolidation process of a contextual fear memory.

Section snippets

Animals

Adult male Wistar rats provided by the Facultad de Veterinaria, Universidad Nacional de La Plata weighing 270–300 g at the start of the experiments were used. All animals were housed in standards laboratory Plexiglas cages in groups of three per cage at the animal colony of the Department of Pharmacology of the Facultad de Ciencias Químicas, and left without manipulation for 2 weeks for acclimation. Food and water were available ad libitum. Animals were maintained on a 12-h light/dark cycle

MDZ does not disrupt contextual fear memory when administered shortly following the training session

As can be seen in Fig. 1 rats that received systemic injection of MDZ displayed similar levels of freezing than animals injected with SAL immediately after conditioning. Analysis revealed no difference between the groups [F(1,20)=1.18, P=0.29].

MDZ disrupts contextual fear memory when given shortly after reminder

Fig. 2b and 2c depict freezing behavior assessed in animals whether subjected to the retrieval session or not. As shown in Fig. 2b both groups of rats (SAL and MDZ) showed a comparable freezing behavior during reactivation. Rats injected with MDZ shortly

Discussion

The main goal of the current study was to evaluate the effect of systemic MDZ administered after a reactivation procedure on the reconsolidation of a contextual fear memory. As expected, rats exposed to a context previously associated with footshock displayed considerable levels of freezing when exposed to test 1. These findings extend and confirm evidence from this and other laboratories demonstrating a reliable conditioned freezing response through the use of a contextual fear learning

Conclusion

In summary, the present data strongly suggest that BDZ administered shortly after the reactivation of an early fear memory with an appropriate cue (training context) disrupts memory reconsolidation. If these evidences are confirmed in humans, the reactivation of a “traumatic memory” through the presentation of a selective and appropriate cue could be susceptible of interference by BDZ compounds, becoming an additional tool for the treatment of patients which have experienced severe and

Acknowledgments

This work was supported by grants from SECyT, FONCyT, Agencia Córdoba Ciencia y CONICET to VAM. Thanks are extended to Dolores Trebucq for English technical assistance.

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