- Traumatic experiences can result in long lasting fearful memories.
- Researchers have shown that a specific drug can suppress fearful memories in a mouse model in a previous study.
- In a new study, the researchers have identified the mechanism of this drug.
In a new study, researchers have identified the mechanism of a drug that they previously found could inhibit fearful memories in mice.
The research, published in the journal Frontiers in Behavioral Neuroscience, opens the door to developing a drug that may have the same effect on humans.
If a person experiences a traumatic event, they may have long lasting fearful memories of the event that reduce their quality of life.
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A person with PTSD may be offered talking therapy or medications to help them recover.
Medical News Today spoke with Dr. Carmen Pedraza, Professor of Psychobiology at the University of Malaga, Spain. Dr. Pedraza was not involved in the study.
“Fear is a normal emotional reaction, vital for survival. When a ‘dangerous’ stimulus is paired with a neutral stimulus, a conditioned fear response can be generated, the extinction of which — when the stimulus that triggered the fear response is not present — is essential for emotional regulation,” according to Dr. Pedraza.
She says that the development of phobias, panic disorders, and PTSD has been linked to failure to properly regulate fear responses, and “fear extinction” is the focus of therapeutic interventions used in treating these disorders.
“The amygdala and the prefrontal cortex are two key structures in the brain circuitry involved in emotional regulation. Results from human and animal studies suggest that disruption of this circuit is important for the development of fear extinction disorders and predicts individual differences in emotion regulation,” Dr. Pedraza explained. “Drugs that modulate this circuit may be a good therapeutic strategy for the treatment of these disorders.”
According to Prof. Akiyoshi Saitoh of the Department of Pharmacy at Tokyo University of Science and the study’s lead author, new drugs are crucial to improving treatment for fearful memories.
“There is currently no effective treatment for fear memory. Monoamine antidepressants are often used, but they have problems such as inadequate treatment satisfaction, the long time required for the onset of therapeutic effect, and side effects that precede the therapeutic effect,” said Prof. Saitoh.
He added that developing “new psychotropic drugs with different mechanisms of action from existing drugs” is necessary to solve these problems.
Dr. Pedraza agreed.
“Several compounds are currently available that facilitate extinction but are not free from adverse effects.”
“The [present] study focuses on the neurobiological mechanisms responsible for the beneficial effect on [the] extinction of KNT-127, a selective agonist of one of the opioid receptors, the δ-opioid receptor, which acts through different signaling pathways in the amygdala and the infralimbic cortex of the prefrontal cortex.”
“This drug may provide an alternative to available treatments,” said Dr. Pedraza.
In the study, the researchers exposed mice to a fear conditioning test. They gave the mice a mild electric shock in response to a conditioned stimulus, prompting a conditioned fear response.
The mice were then split into two groups. One group received the drug KNT-127 to various parts of the brain, while the other acted as a control.
When exposed to the conditioning chamber where they received the electric shocks, the mice that received the drug in the basolateral nucleus of the amygdala and the infralimbic subregions of the prefrontal cortex showed significantly less fear response.
The finding may mean KNT-127 could be developed into a drug applicable to humans. However, Dr. Pedraza cautioned there was a long way to go before this could become a reality.
“Animal models of psychopathological disorders are useful to gain insight into the neurobiological mechanisms of these disorders and are the starting point for the development of further studies and clinical trials for the commercialization of drugs for therapeutic purposes.”
“However, there are several considerations to take into account in order to know the real scope of this study for the treatment of fear-related disorders. Decrement of fear conditioning generally is not permanent: after learning to extinguish fear, it is common for the fear response to reappear, and sometimes it can be strengthened. Moreover, extinction is cue specific,” she said.
To know the true efficacy of such a new treatment option, Dr. Pedraza noted that it would be necessary to extend pre-clinical trials to situations where the “reappearance of extinguished fear responses is observed.”
“It would also be necessary to study the long-term effect, given that sometimes spontaneous recovery of the fear response occurs,” she explained. “KNT-127 may be a promising therapeutic alternative to available treatments, but there is still a long way to go.”