Stressful experiences can increase the chances of anxiety or depression in vulnerable people.

Recent research has suggested that in addition to regulating cell death and differentiation, p38 MAPK is also involved in other neuronal processes, including stress-induced behavioral responses. "Although the cellular and molecular basis for these behavioral actions is not known, one possible site of action is the serotonergic neurons, because this transmitter system has a well-established role in the regulation of mood," explains study author Dr. Michael R. Bruchas. Dr. Bruchas, coauthor Dr. Charles Chavkin, and their colleagues at the University of Washington in Seattle studied the effects of p38alpha MAPK in serotonergic neurons in the dorsal raphe nucleus, the primary source of serotonin in the brain.
In mouse models of stress-induced depression-like behaviors, selective deletion of p38alpha MAPK from serotonin-producing neurons in the dorsal raphe nucleus resulted in mice that did not exhibit depression-like or drug-relapse-like behaviors in response to stress. This was in direct contrast to mice with typical p38alpha MAPK activity. The researchers went on to show that activation of p38alpha MAPK by kappa opioid receptors increased the rate of serotonin reuptake. These findings suggest that stress initiates a cascade of events in which p38alpha MAPK reduces the amount of serotonin available in the brain, leading to depression-like behaviors.
"Our data demonstrate that p38alpha expression in serotonin neural circuits is required for local regulatory control of serotonin transport that ultimately controls behavioral responses, including social avoidance, relapse of drug seeking, and the dysphoria-like responses," concludes Dr. Chavkin. "These results are important because they implicate a critical requirement for p38alpha MAPK signaling in serotonin neuronal function during stress and demonstrate that p38alpha MAPK, in spite of its ubiquitous expression profile, has the ability to specifically regulate selected downstream targets to shape behavioral output. Further, activation of this system by kappa opioid receptors may represent a novel therapeutic target to promote stress resilience."
Source-Eurekalert