Using a classical model of depression, this study investigated the effects of social defeat stress on emotional behaviors, on cognitive flexibility in the attentional set-shifting task (AST), and on the expression of extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK2) and their downstream signaling molecules cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in two subregions of the PFC, the medial prefrontal cortex (mPFC), and the orbitofrontal cortex (OFC).
The results of this study suggest that palmatine can alleviate the comorbidity of DNP and DP by inhibiting the expression of P2X<sub>7</sub> receptors in the hippocampus, and its action may be related to suppression of the phosphorylation of ERK1/2 and the release of TNF-α and IL-1β in the hippocampus.
These findings provide evidence that the FGF2-ERK1/2 pathway is involved in the pathophysiology of depressive-like behaviors, and manipulating the neurogenesis pathway is a viable therapeutic approach to inflammation-associated depression.
Although ERK1/2 has been proposed as a common mediator of antidepressant action in naive rodents, it remains to be determined whether the ERK1/2 pathway plays a role in depressive disorder.
The intracellular factors by which ADTs and glucocorticoids, causal factors in depression, regulate depression-like behavior remain unclear, but extracellular signal-regulated kinase 1/2 (ERK1/2), upstream of CREB, is a likely candidate.
Given the role of MAP kinases in various physiological functions and gene expression, alterations in p44/42 MAP kinase activation and expression of ERK1/2 may contribute significantly to the pathophysiology of depressive disorders.