CONICET | Buscador de Institutos y Recursos Humanos

Background: Withdrawal from chronic ethanol facilitates the formation of contextual fear memory and delays the onsetto extinction, with its retrieval promoting an increase in ethanol consumption. Consequently, manipulations aimed toreduce these aversive memories, may be beneficial in the treatment of alcohol discontinuation symptoms. Related to this,pharmacological memory reconsolidation blockade has received greater attention due to its therapeutic potential.Methods: Here, we examined the effect of post-reactivation amnestic treatments such as Midazolam (MDZ, 3 mg/kg i.p) andPropranolol (PROP, 5 mg/kg i.p) on contextual fear memory reconsolidation in ethanol- withdrawn (ETOH) rats. Next, we examinedwhether the activation of N-methyl-D-aspartate (NMDA) receptors induced by d-cycloserine (DCS, 5 mg/kg i.p., a NMDA partialagonist) before memory reactivation can facilitate the disruptive effect of PROP and MDZ on fear memory in ETOH rats.Results: We observed a resistance to the disruptive effect of both MDZ and PROP following memory reactivation. Althoughintra-basolateral amygdala (BLA; 1.25 ug/side) and systemic PROP administration attenuated fear memory in DCS pre-treatedETOH rats, DCS/MDZ treatment did not affect memory in these animals. Finally, a decrease of both total and surface proteinexpression of the α1 GABAA receptor (GABAA-R) subunit in BLA was found in the ETOH rats.Conclusions: Ethanol withdrawal facilitated the formation of fear memory resistant to labilization post-reactivation.DCS administration promoted the disruptive effect of PROP on memory reconsolidation in ETOH rats. The resistance toMDZ?s disruptive effect on fear memory reconsolidation may be, at least in part, associated with changes in the GABAA-Rcomposition induced by chronic ethanol administration/withdrawal.