Efecto de la administración de moduladores alostéricos negativos selectivos para la subunidad GABA[sub]A[alfa]5 sobre los procesos cognitivos implicados en las alteraciones de aprendizaje y memoria de un modelo de síndrome de Down

Abstract

In Down Syndrome (DS) there are several structural and functional abnormalities in the Central Nervous System (CNS). Among them the most notable is intellectual disability. Among the possible causes of these cognitive alterations it has been proposed that one of the most relevant could be the overinhibition mediated by the GABAA receptor. Therefore, the effect of the administration of selective negative allosteric modulators (NAMs) for the GABAAα5 subunit on the cognitive and behavioral deficits of the murine DS model, Ts65Dn (TS), was evaluated in this study. The pharmacological blockade of the GABAAα5 receptor had prognostic effects, further improving the processes of coding and consolidation of information in procedural learning and reference memory, the process of consolidation of working memory and the processes of coding, consolidation and retrieval of Information in the spatial memory, without provoking adverse side effects, nor altering the sensorimotor capacities.