PTSD cure? Scientists say the brain can learn to be fearless

BOCHUM, Germany — People who have experienced traumatic events may develop a lasting fear response that hinders their quality of life. The messaging chemical serotonin plays a key role in how fear and anxiety develop. However, German researchers are now using this information to help people “learn” to become fearless.

This long-lasting fear response, more commonly referred to as post-traumatic stress disorder (PTSD), requires significant effort from the ones who have the condition to “unlearn” their deep fears. Often, environmental stimuli that ends up becoming overwhelming or anxiety-inducing triggers this traumatic mental state. As a result, scientists have begun to shift their focus to extinction learning, which describes the decrease in a learned behavior in response to an external stimulus.

To explore serotonin’s possible role in helping with this, a team from Ruhr University Bochum used genetically-engineered mice that were missing a serotonin receptor, called the 5-HT2C receptor. Within a day, the mice learned to associate a specific sound with an unpleasant stimulus.

“As a result of this learning process, on the following day they showed a fear response that was characterized by a motionless pause as soon as the tone was played, which we refer to as ‘freezing,’” explains Katharina Spoida in a university release.

After this, the researchers repeatedly played the sound for the mice without responding with the fear-inducing electrical stimulus.

“Interestingly, we noticed that knock-out mice learned much faster that the tone does not predict the fear stimulus than mice who lacked this specific genetic modification,” says Katharina Spoida. “Consequently, it looks like the absence of the serotonin receptor provides an advantage for extinction learning.”

The findings could improve antidepressant drugs

The researchers then explored these findings in more depth. In doing so, they found that the mice experienced changes in neuronal activity in two different parts of the brain, the dorsal raphe nucleus (DRN) and bed nucleus of the stria terminalis (BNST). Scientists consider the DRN the main area for serotonin production and the BNST is part of the extended amygdala, which is responsible for emotional processing in response to stimuli.

“In the knock-out mice, we first found an increased basal activity in certain serotonin-producing cells of the dorsal raphe nucleus. In a subsequent step, we showed that the absence of the receptor also alters neuronal activity in two subnuclei of the BNST, which ultimately supports extinction learning,” describes first author Sandra Süß.

These findings suggest that a significant relationship may exist between these two areas, helping to improve extinction learning outcomes. The work may also open doors for better understanding how selective serotonin reuptake inhibitors (SSRIs), a specific class of antidepressant drugs, affect these brain regions.

“Taking these drugs over a prolonged period of time causes the relevant receptor to become less responsive to serotonin, similar to our knock-out model. Therefore, we assume that the changes we’ve described could be essential for the positive effect of SSRIs,” adds Süß.

The findings are published in the journal Translational Psychiatry.

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