14 DAY TRIAL // A group of researchers at the Washington University in St. Louis School of Medicine (WUSM) and the University of Washington in Seattle (UWS) say that they manged to identify a new potential therapeutic target, that could be used to treat depression, anxiety and addiction.
Experts arrived at this conclusion following studies seeking to determine how stress is involved in controlling mood and predispositions towards addiction. The investigations – conducted on unsuspecting mice – provide a relevant research proxy for the human brain.
Together, the joint team was able to determine that the cascade of stress-related impulses flowing through neurons is largely responsible for a wide array of negative health effects, including depression, anxiety and the inclination to use drugs.
By blocking this cascade, the researchers hypothesize, it may become possible to eliminate the neurological background on which these behaviors and conditions are founded. What this implies is that treating the disorders may circumvent the need for drugs affecting neurotransmitters.
As far as depression goes, certain commonly-used drugs are known to have significant side-effects, but doctors don't have a choice but to use them. The new study provides an alternative means to go about trying to cure these conditions.
Details of the research effort were published in the August 11 issue of the respected scientific journal Neuron. The team explains how it set up an experiment seeking to discover the molecules that make lab mice predisposed to exhibiting depression- and addiction-like symptoms.
Whenever the tiny rodents were exposed to stress, their bodies began producing larger amounts of a protein called p38α mitogen-activated protein kinase (MAPK). The chemical then went on to influence the overall behavior the mice exhibited, making them more depressed and likely to become addicted.
In-depth investigations on this correlation revealed that p38α MAPK is activated in order to regulate the activity of the key neurotransmitter serotonin – a chemical known to control mood. The protein was activated by structures kappa-opioid receptors, located on neurons on serotonin's neural pathway.
“We call these responses ‘depression-like’ and ‘addiction-like’ behaviors because we can’t ask mice if they’re addicted or sad,” explains WUSM assistant professor of anesthesiology and of anatomy and neurobiology Michael R. Bruchas, PhD, the first author of the study.
“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,” the investigator goes on to say.
“It will be important to determine whether this pathway is conserved for drugs of abuse other than cocaine. If so it will further highlight the importance of working with chemists to target this pathway for potential therapies,” Bruchas adds.
UWS professor of pharmacology Charles Chavkin, PhD, was the senior investigator on the research.