Researchers at Washinton University think they’ve identified a protein in the brain that if blocked or manipulated, can also block pain, depression and addiction.
Researchers from St. Louis and Seattle are studying mice to understand how stress affects mood and motivation for drug use.
Michael Bruchas at Washington University School of Medicine says tests on mice who were exposed to stress tended to socially withdraw and return to where they had been given cocaine injections.
“We call these responses ‘depression-like’ and ‘addiction-like’ behaviors because we can’t ask mice if they’re addicted or sad,” Bruchas says. “But just as depressed people often withdraw from social interactions, stressed mice do the same thing. We also observed that stressed mice return more often to the place where they received cocaine.”
Bruchas says this test only dealt with cocaine, so it would need to be re-created to see if it works with nicotine, amphetamines and heroin. However, he says he and his team are hoping these studies can eventually benefit society by helping curb addictions, block pain and can help modify current anti-depressants so they’re more specific to individual needs.
“We put a mouse into an enclosure with an ‘aggressor’ mouse,” Bruchas says. “Some mice, like some humans, are more dominant and aggressive. When a non-aggressive mouse is put into a cage with an aggressive animal, that aggression causes stress similar to what we might see in an adult human working for a difficult boss or a teenager who has to deal with a bully at school.”
The team reports in the August issue of the journal Neuron that in mice exposed to stress, a protein called p38a mitogen-activated protein kinase (MAPK) influences the animal’s behavior, contributing to depression-like symptoms and risk for addiction.
Bruchas says the studies on mice models show that p38a 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 p38a MAPK, which then interacts with the serotonin transporter in the cells to reduce the amount of available serotonin.
The study was funded by the National Intitute on Drug Abuse.
Bruchas, PhD, is the assistant professor of anesthesiology and of anatomy and neurobiology at Washington University School of Medicine in St. Louis. The senior investigator is Charles Chavkin, PhD, professor of pharmacology at the University of Washington in Seattle.
While working in Chavkin’s laboratory at the University of Washington, Bruchas and his colleagues studied mice exposed to what they call social defeat stress.
Just as interacting with a “bully” mouse is similar to dealing with stressful environments, Bruchas and Chavkin say the cascade of events in the brain that contributes to serotonin reduction appears to be similar in both mice and humans.
“When people take antidepressant drugs called selective serotonin reuptake inhibitors, or SSRIs, to relieve depression, the drugs act on a cellular pump called the serotonin transporter, and this results in more serotonin in the brain,” Bruchas says. “We think that the involvement of the p38a protein and kappa-opioid receptors represents an important finding in figuring out how it is that cells regulate depressive and addictive behaviors.”
Washington University published the article here: http://listresponse.wustl.edu/trk/click?ref=zthfgip7o_0-1972x3187cx136&