P99. Role of Α5-Gabaa Receptor Positive Allosteric Modulation on Cognitive Functions and Neurotrophic Effects Across Animal Models

Reduced GABA/somatostatin (SST) signaling is reported in psychiatric, stress-related and neurodegenerative disorders. SST+ interneurons from cortical layers and the hippocampus inhibit the dendrites of excitatory neurons, largely through α5-containing GABAA receptors (α5-GABAAR). Recently, we showed that an α5-positive allosteric modulator (α5-PAM) alleviates working memory deficits and reverses neuronal atrophy in old mice. Here, we investigated the behavioral and neurotrophic effects of this α5-PAM in animal models of aging, chronic stress, and β-amyloid load.