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Breakthrough Discovery Unveils Potential For Panic Disorder Drugs

Scientists identify brain circuit in mice that could alleviate panic symptoms, offering hope for new therapeutics.

A breakthrough discovery could lead to new drugs that prevent people from suffering panic attacks. Researchers in the US observing panic attacks in mice identified a brain circuit of specialized neurons that could be controlled to mediate panic disorder.


The scientists located an area of the brain involved in generating panic and bringing about emotional and physical changes. The research team, from the Salk Institute for Biological Studies, also found that by inhibiting certain signals they could reduce panic symptoms – offering hope for the development of drugs to alleviate panic disorder.

The Salk scientists, based in California, set out to create a map of the regions and connections in the brain that mediate panic attacks, in order to offer effective therapeutics in the future.


People suffering from panic disorder experience frequent and unexpected attacks which trigger symptoms of overwhelming fear, sweaty palms, shortness of breath and a rapid heart rate. To begin drawing their map, the researchers looked at a part of the brain called the lateral parabrachial nucleus (PBL), located in part of the brain stem known as its alarm center.


This small brainstem area, called the pons, also controls our breathing, heart rate, and body temperature. The scientists found the PBL was implicated in generating panic and bringing about emotional and physical changes. They also discovered that this area of the brain produces the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide), known as the master regulator of stress responses.


However, the link between these elements was still unclear, so the team turned to experiments in mice to confirm and expand their proposed map. Sukjae Kang, a senior research associate at Salk and co-first author of the study, explained: “Emotional and stress-related behaviors have been associated with PACAP-expressing neurons in the past.

“By mimicking panic attacks in the mice, we were able to watch those neurons’ activity and discover a unique connection between the PACAP brain circuit and panic disorde,” said Kang. 


In observing the brains of mice during panic attacks, the researchers found that PACAP-expressing neurons became activated. Once activated, they release PACAP neuropeptide messenger to another part of the brain called the dorsal raphe, where neurons expressing PACAP receptors live.

The released PACAP messengers activate those receptor neurons, thereby producing panic-associated behavioral and physical symptoms in the mice.

This newly discovered connection between panic disorder and the PACAP brain circuit was an important step in mapping panic disorder in the brain. The team additionally found that by inhibiting PACAP signaling, they could disrupt the flow of PACAP neuropeptides and reduce panic symptoms – a promising finding for the future development of panic disorder-specific therapeutics.


Dr. Sung Han, senior author of the study and an associate professor at Salk, says that despite panic disorder’s categorization as an anxiety disorder, there are many ways in which anxiety and panic differ. Panic, for example, induces physical symptoms such as shortness of breath, a rapid heart rate, sweating and nausea – whereas anxiety does not induce these symptoms.


Panic attacks are also uncontrollable and often spontaneous, whilst other anxiety disorders such as post-traumatic stress disorder (PTSD) are more memory-based and have predictable triggers.


Dr Han explains that these differences are why it is crucial to construct this panic disorder brain map, so researchers can create therapeutics specially tailored to panic disorder.

“We found that the activity of PACAP-producing neurons in the brain’s parabrachial nucleus is inhibited during anxiety conditions and traumatic memory events,” he said.


“The mouse’s amygdala actually directly inhibits those neurons. “Because anxiety seems to be operating conversely to the panic brain circuit, it would be interesting to look at the interaction between anxiety and panic, since we need to explain now how people with anxiety disorder have a higher tendency to experience panic attack.”


Dr Han’s team now hopes to explore PACAP-expressing neurons and PACAP neuropeptides as druggable targets for panic disorder. The team behind the study, published in the journal Nature Neuroscience, also hopes to further build out their map of panic disorder in the brain to see where the PACAP receptor-producing neurons in the dorsal raphe send their signals, and how other anxiety-related brain areas interact with the PACAP panic system.


Produced in association with SWNS Talker

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