Researchers studying mice are getting closer to understanding how stress affects mood and motivation for drugs.
According to the researchers, blocking the stress cascade in brain cells may help reduce the effects of stress, which can include anxiety, depression and the pursuit of addictive drugs.
A research team from St. Louis and Seattle reports in the Aug. 11 issue of the journal Neuron that in mice exposed to stress, a protein called p38α mitogen-activated protein kinase (MAPK) influences the animal’s behavior, contributing to depression-like symptoms and risk for addiction.
The first author is Michael R. Bruchas, PhD, assistant professor of anesthesiology and of anatomy and neurobiology at Washington University School of Medicine in St. Louis, and the senior investigator is Charles Chavkin, PhD, professor of pharmacology at the University of Washington in Seattle.
The researchers demonstrate that p38α MAPK protein is activated by kappa-opioid receptors on neurons to regulate serotonin, a key neurotransmitter that helps regulate mood. When exposed to stress, the brain releases hormones that specifically interact with kappa-opioid receptors on neurons. Those receptors, in turn, activate p38α MAPK, which then interacts with the serotonin transporter in the cells to reduce the amount of available serotonin.
In this study, funded by the National Institute on Drug Abuse, the researchers looked at a brain region, called the dorsal raphe nucleus, where many stress-related factors and serotonin converge. They found that after stress exposure, mouse brains activate p38α MAPK, lowering serotonin levels and triggering depression-like behavior as well as drug-seeking behavior in the mice.
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