IFEC   20925
INSTITUTO DE FARMACOLOGIA EXPERIMENTAL DE CORDOBA
Unidad Ejecutora - UE
artículos
Título:
The Disruptive Effect of Midazolam on Fear Memory Reconsolidation: Decisive Influence of Reactivation Time Span and Memory Age
Autor/es:
SILVIA G. BUSTOS, HÉCTOR MALDONADO AND VÍCTOR A. MOLINA.
Revista:
NEUROPSYCHOPHARMACOLOGY
Editorial:
Nature Publishing Group
Referencias:
Lugar: New York; Año: 2009 vol. 34 p. 446 - 457
ISSN:
0893-133X
Resumen:
Benzodiazepine (BDZ) administered shortly after retrieval disrupts the reconsolidation of fear memory. In this research, we explored
the way in which different factors that limit the emergence of such process may affect BDZs disruptive effect on fear memory
reconsolidation. Animals were conditioned in a contextual fear paradigm; the consolidated memory was reactivated by exposure to the
associated context for different periods of time that were followed by midazolam (MDZ) administration. We also studied MDZ amnesic
effect after reactivating fear memories of several ages. We finally analyzed the effectiveness of different MDZ doses in preventing the
reconsolidation of different age fear memories. The memory trace was disrupted following MDZ when the reactivation session lasted
35 min but it was not after a briefer 1-min reactivation period. Over a 10-min reactivation session, all animals gradually reduced their
fear response, which indicates the emergence of the extinction process. When tested, MDZ rats exhibited a robust fear, suggesting that
MDZ impaired the consolidation of extinction. In a 3-min reactivation session, MDZ (11.5 mg/kg) prevented the reconsolidation of
recently acquired memories. A 21-day-old fear memory was only vulnerable to MDZ at a 1.5 mg/kg dose with a reactivation session of 5
and not 3 min, whereas a 36-day-old memory was only disrupted with a higher MDZ dose (3 mg/kg) regardless of the reactivation trials
duration. This study demonstrated MDZs interference on fear-memory reconsolidation within a relatively short reactivation period in
recently acquired memories. Over longer reexposure, MDZ disrupts the consolidation of extinction. A longer duration of the reexposure
session, as well as higher MDZ doses, is required to prevent the reconsolidation process of remote fear memories.