Effect of chronic unpredictable mild stress on the expression profile of serotonin receptors in rats and mice: a meta-analysis

Chronic-stress-induced depression is recognized as a widespread public health concern. Selective serotonin reuptake inhibitors (SSRIs) have been the most common treatment for this illness. However, the role of 5-hydroxytryptamine (5-HT) receptor subtypes in stress-induced depression remains unclear. Evidence from Animal studies has reported a variety of results regarding the effects of chronic unpredictable mild stress (CUMS) on serotonin signaling pathways and 5-HT receptor subtypes. This divergence may rely on differences in protocols, methods, and studied pathways. Thus, the aim of this systematic review was to weigh the currently available findings regarding serotonin receptor changes in animal models of CUMS. Overall, our meta-analysis results showed the association of altered expression of 5-HT1A receptors in the frontal cortex and 5-HT2A receptors both in the whole cortex and the hypothalamus of rats following CUMS. Moreover, by using a qualitative-structured analysis and the application of risk-of-bias tools, we identified possible sources of data variation between the studied literature, which should be taken into account in future animal studies of chronic-stress induced depression.