Phosphodiesterase 5 inhibition during reconsolidation triggers fear memory generalization

Fear generalization, a lack of capacity to discriminate between safe and unsafe environments, is a hallmark of psychiatric disorders such as posttraumatic stress disorder. Context discrimination is facilitated by the pattern separation process, which minimizes overlap between neuronal activity patterns that represent similar experiences. Generalization might be a consequence of recent memory overconsolidation; or systems consolidation, dependent on the passage of time. After retrieval, memory can render labile and then reconsolidate. Reconsolidation and consolidation share several mechanisms. During consolidation, stimulating the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway promotes fear memory generalization. The cGMP concentration is regulated by phosphodiesterase 5 (PDE5), an enzyme that hydrolyzes cGMP, limiting its signaling pathway. Whether PDE5 activity during reconsolidation of recent memory is involved in fear memory generalization is unknown.