Investigators believe the new approach has many advantages over the current method of using ‘receptor-binding’ opioid drugs like morphine, which have major side effects.
Fear and anxiety are natural responses that help defend us against harm. The feelings are largely controlled via circuits of interconnected nerve cells and activity in a specific brain region (the amygdala) that allow neurons to pass electrical or chemical signals to each other.
Specialized neural circuits control these emotions, but disturbances in the circuits can cause prolonged and disabling emotional responses that are out of proportion to threatening events.
These disturbances are thought to underlie many anxiety disorders such as phobias and post-traumatic stress disorder, which affect millions each year.
Anxiety disorders affect approx. 14 percent of the population but are poorly managed by commonly prescribed medications such as benzodiazepines and 5HT-reuptake inhibitors.
“These drugs weren’t developed to treat anxiety but they’re widely used because of chance findings suggesting their clinical usefulness,” says the University of Sydney’s Associate Professor Elena Bagley, who led the research.
“Many experts agree that better anxiety treatments will come when science uncovers how the neural circuits and endogenous or naturally occurring opioids regulate fear and anxiety.
“The precise action of these natural opioids in the brain is poorly understood, but better insights are critical because these opioids control how we acquire and store fear memories and regulate our emotional responses once a threat has passed.”
As published in Nature Communications, experiments in mice have shown that “deleting” the natural opioid encephalin — which is heavily expressed in the brain’s amygdala — increases their fear, anxiety, and aggressiveness.
By contrast, increasing enkephalin or reducing its breakdown reduces these behaviors.
While this effect of enkephalin suggests that it is anxiety-inhibiting, when it binds to different receptors in the amygdala, it exerts opposing effects, depending on which one it binds to.
For example, when it binds to the mu-opioid receptor, enkephalin promotes anxiety, but when it binds to the delta-opioid receptor, it inhibits it.
“Given this complexity, understanding the cellular actions of natural opioids at these two receptors is critical if we hope to use opioid-related medications for emotional issues,” says Dr Bagley.
“Our findings show that opioids produced and released by our own brain cells strongly regulate these critical neural circuits that are important for fear responses.
“We also show that we could boost the actions of these endogenous opioids using a novel pharmacological approach.”
Source: University of Sydney