Cognitive Effects of 5-HT7 Receptor Blockade in Rats Exposed to Chronic Stress: Role of Prefrontal Cortex Microglial Activity and Canonical Wnt/β-Catenin Signaling Pathway

Abstract

The neurobiology underlying depression and the associated cognitive dysfunction has not yet been fully identified. Additionally, the currently available antidepressants have significant limitation including persistent cognitive deficits even after improvement of depressive symptoms. Significant efforts have been directed toward identifying novel therapeutic targets for management of cognitive dysfunction associated with depression. 5HT7 receptor is a promising target as its blockade has procognitive effects. Additionally it modulates the activity of microglia and the Wnt/β-catenin pathway which are implicated in the pathogenesis of depression and the associated cognitive dysfunction.

Accordingly, our study was designed to evaluate whether 5HT7 blockade by amisulpride may improve the depressive like behavior and the cognitive dysfunction induced by the UCMS model of depression in rats. Furthermore, we would investigate the effect of the model and the treatment on the Wnt/β-catenin pathway and microglial activation in the PFC.