Vulnerable people are consistently under the spells of anxiety or depression clubbed with stress that can enhance addictive drug consumption. The mechanisms associating stress with human behaviors have not been fully explored and understood. However, molecular events that may have caused stress susceptibility in people have been defined through the development and use of animal models for certain characteristic behaviors.
These studies aim at improving resilience to stress by identifying prospective new therapeutics. In a new research published in the August 11 issue of the journal Neuron, researchers reveal that cellular stress, regulation of mood disorders, and addiction risk can be credited to a formerly unacknowledged mitogen-activated protein kinase called p38alpha.
According to recent research, p38 MAPK has a role in other neuronal processes, including stress-induced behavioral responses, together with being involved in the regulation of cell death and differentiation. Study author Dr. Michael R. Bruchas explained, “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.” The impact of p38alpha MAPK in serotonergic neurons in the dorsal raphe nucleus, the primary brain-serotonin source of serotonin, was studied by author Dr. Bruchas, coauthor Dr. Charles Chavkin, and their colleagues at the University of Washington in Seattle.
Mouse models displaying stress-induced depression-like behaviors were used to create mice that did not exhibit depression-like or drug-relapse-like behaviors in response to stress. This was achieved by selectively deleting p38alpha MAPK from serotonin-producing neurons in the dorsal raphe nucleus.
Mice with typical p38alpha MAPK activity were dissimilar to these. Researchers explained that an increased serotonin reuptake was caused by activation of p38alpha MAPK by kappa opioid receptors. According to these findings, a cascade of events is initiated by stress, wherein depression-like behaviors are caused when p38alpha MAPK decreases the amount of serotonin available in the brain.
To conclude, Dr. Chavkin said, “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. 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.”