AsianScientist (Mar. 4, 2020) – A research group in Japan has found that opiates mask fear memory and could be effective for the treatment of anxiety disorders. Their findings are published in the journal Neuropharmacology.
Treating individuals with anxiety problems such as phobias and post-traumatic stress disorder often involve helping them overcome fear. Some opioid compounds, called delta opioid receptor (DOP) agonists, are known to alleviate the overwhelming fear and anxiousness in patients.
In the present study, scientists led by Professor Akiyoshi Saitoh at the Tokyo University of Science, Japan, tested two DOP agonists in mice subjected to a fear conditioning test. On the first day of the experiment, the mice were placed in conditioning chambers and they were inflicted with a shock to the foot at regular intervals. This was designed to induce fear in the mice, which would henceforth associate the chamber with painful foot shocks.
On the second day, one group of fear-conditioned mice were given saline (the control group) while the other was given DOP agonists KNT-127 or SNC80. All the mice were subsequently released into the conditioning chamber once again. They were not given any more foot shocks, but the researchers observed the behavior of the mice over the next day.
Saitoh’s group reported that on the second day of the experiment, the mice receiving KNT-127 or SNC80 showed significantly less ‘freezing’ behavior, indicating that they were less paralyzed by fear. On day three, the mice on KNT-127 showed reduced freezing behavior, but those on SNC80 did not.
The scientists also examined the effects of these drugs on the activities of enzymes and pathways in the brain that are known to drive the masking of fear memory. They found that KNT-127 increased the levels of activation of an enzyme called ERK, which is involved in the ability to overcome fear conditioning in parts of the brain. Taken together, these results suggest that although both KNT-127 and SNC80 reduce conditioned fear, only KNT-127 helps suppress contextual fear memory.
Saitoh noted that the fear conditioning test used in this study is also a model of PTSD. He added that currently prescribed medication for PTSD takes several weeks to have therapeutic effects and do not produce satisfactorily positive patient outcomes.
“There are also no potential breakthrough therapies for such disorders,” he said. “Our study shows that DOP agonists, when used in combination with cognitive behavioral therapy, can enhance the efficacy of treatment for anxiety disorders. It offers hope for the realization of a safe and effective new mode of therapy for PTSD and other related psychiatric disorders.”
The article can be found at: Yamada et al. (2019) Selective Agonists of the δ-opioid receptor, KNT-127 and SNC80, Act Differentially on Extinction Learning of Contextual Fear Memory in Mice.
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Source: Tokyo University of Science; Photo: Shutterstock.
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