title: Stress-induced resistance to the fear memory labilization/reconsolidation process. Involvement of the basolateral amygdala complex.
abstract: Consolidated memories can enter into a labile state after reactivation followed by a restabilization process defined as reconsolidation. This process can be interfered with Midazolam (MDZ), a positive allosteric modulator of the GABA-A receptor. The present study has evaluated the influence of prior stress on MDZ's interfering effect. We also assessed the influence of both systemic and intra-basolateral amygdala (BLA) infusion of d-cycloserine (DCS), a partial agonist of the NMDA receptors, on the MDZ effect in previously stressed rats. Furthermore, we analyzed the effect of stress on the expression of Zif-268 and the GluN2B sites, two molecular markers of the labilization/reconsolidation process, following reactivation. The results revealed that prior stress resulted into a memory trace that was insensitive to the MDZ impairing effect. Both systemic and intra-BLA DCS administration previous to reactivation restored MDZ's disruptive effect on memory reconsolidation in stressed animals. Further, reactivation enhanced Zif-268 expression in the BLA in control unstressed rats, whereas no elevation was observed in stressed animals. In agreement with the behavioral findings, DCS restored the increased level of Zif-268 expression in the BLA in stressed animals. Moreover, memory reactivation in unstressed animals elevated GluN2B expression in the BLA, thus suggesting that this effect is involved in memory destabilization, whereas stressed animals did not reveal any changes. These findings are consistent with resistance to the MDZ effect in these rats, indicating that stress exposure prevents the onset of destabilization following reactivation. In summary, prior stress limited both the occurrence of the reactivation-induced destabilization and restabilization.
authors.affiliation: IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Pablo Javier
authors.initials: PJ
authors.lastname: Espejo
authors.affiliation: IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Ortiz
authors.affiliation: IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Irene Delia
authors.initials: ID
authors.lastname: Martijena
authors.affiliation: IFEC-CONICET, Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. Electronic address: vmolina@fcq.unc.edu.ar.
authors.forename: Victor Alejandro
authors.initials: VA
authors.lastname: Molina
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis; D005239:Fear / Q000502:physiology* / Q000523:psychology; D008297:Male; D000069077:Memory Consolidation / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Amygdala; GluN2B; Midazolam; Reconsolidation; Stress; Zif-268; d-cycloserine