Previous stress attenuates the susceptibility to Midazolam’s disruptive effect on fear memory reconsolidation: Influence of pre-reactivation D-cycloserine administration

BUSTOS SG, GIACHERO M, MALDONADO H, MOLINA VA

NEUROPSYCHOPHARMACOLOGY

NATURE PUBLISHING GROUP

Año: 2010 vol. 35 p. 1097 - 1108

0893-133X

It is well known that, under certain boundary conditions, the retrieval of a stable consolidated memory results into a labile one. During this unstable phase, memory can be vulnerable to interference by a number of pharmacological agents, including benzodiazepines. One of the goals of the present study was to evaluate the vulnerability to midazolam (MDZ) after reactivation of recent and remote contextual fear memories in animals that experienced a stressful situation prior to learning.  Animals were subjected to a restraint session and trained in a contextual fear paradigm the following day; consolidated memories were reactivated at different times following learning and different MDZ doses (1.5, 3.0 mg/kg) were administered to rats after reactivation. Our results show that MDZ did not affect memory reconsolidation in older-than-one-day memories of stressed animals, not even after the administration of a higher MDZ dose and a longer reactivation session (5 min). In contrast, MDZ was effective in blocking reconsolidation at all memory ages in unstressed animals. In addition, the current research investigated whether activating NMDA sites prior to reactivation promotes the destabilization of resistant memories such as those of stressed animals. We tested the influence of pre-reactivation D-cycloserine (DCS), a partial NMDA agonist, on MDZ’s effect on fear memory reconsolidation in stressed animals. Our findings indicate that DCS prior to reactivation promotes retrieval-induced lability in resistant memory traces since MDZ-induced memory impairment in stressed rats became evident with pre-reactivation DCS but not after pre-reactivation SAL.