Kappa opioid receptors (KORs) may sound like an obscure fraternity chapter, but they are actually a tiny brain protein at the center of research on ways to treat various mental health conditions. The proteins play a role in releasing neurotransmitters related to pain perception and mood. And in a recent study, scientists discovered the exact cellular mechanism that allows these receptors to drive anxiety. If so, the results could contribute to the development of anxiety and addiction drugs.

KORs are popular among drug developers for their ability to provide pain relief without the potential risk of addiction. Ultimately, the proteins work by inhibiting the release of the neurotransmitter glutamate in the part of the brain that regulates emotions. However, KORs’ potential pharmaceutical uses remain untapped, as scientists are still unsure about how exactly the proteins work. In an effort to better understand KORs' behavior, researchers from the University of North Carolina used knock-out mice, mice that had been genetically designed to have certain genes expressed or repressed, to understand how activating and inactivating KORs affected the animals’ behavior.

The mice had their KORs activated or deactivated before being placed in potentially stressful situations. The team saw significant behavioral differences in the mice that had their KORs activated, when compared to mice whose receptors were disabled.

“When KORs are inactivated, glutamate is released properly and mice showed significant signs of feeling less anxious," lead researcher Dr. Thomas L. Kash said in a recent statement. "But when kappa opioid receptors are activated, this glutamate release associated with 'safety' was tamped down. There were clear signs of more anxiety.”

These signs of anxiety included spending less time in the open arm of a mouse maze and in the center of an open field, Kash told Medical Daily. "When we removed the receptor, mice spent more time in the open arm" — suggesting they were less anxious because it is the "innate activity of mice to stay away from open areas."

Kash said these results suggest that KORs could essentially “shut off an anxiety-reducing pathway in the brain.” What makes the study particularly exciting is the that these KORs are not limited to mouse brains: they also exist in humans.

“While it is quite challenging at this point to say if they work the exact same way in humans, we do know that there are similar homologous structures and connections in the human brain, and that there are also kappa opioid receptors in these structures,” said Kash, who thinks that because of this, the same results are likely to be found in humans.

We all need some level of anxiety because taking it all away would pose a significant health and safety danger. The emotion helps keep us out of harm's way and forces us to prepare for important events. However, for those with anxiety disorder, the feeling is persistent and often interferes with their ability to live a normal life. According to the Anxiety and Depression Association of America, anxiety disorder is an umbrella term for many stress-related mental health conditions, such as panic disorder, social anxiety, and specific phobias like fear of driving.

The ability to use KORs in a medical setting would inevitably give doctors more power over controlling patient's anxiety disorders. This, of course, if further down the line, but not completely far-fetched since several pharmaceutical companies are already working on developing KOR antagonists as a treatment for anxiety and drug abuse.

For now, Kash explains that the next plan of action is to study different forms of anxiety, such as alcohol-induced anxiety. This would help to identify specific neurons associated with the condition, and hence neurons that would be a target for future drug development.

Source:Kash TL, Crowley NA, Bloodgood DW, et al. Dynorphin Controls the Gain Of An Amygdalar Anxiety Circuit. Cell Reports. 2016