Potential New Target for Anxiety-Reducing Drugs Identified – Medscape

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Dr Rob Hicks
March 16, 2022
A novel brain fear mechanism has been identified by neuroscientists who say their discovery paves the way for new anxiety-reducing drugs in the future.
Neuroscientists from the University of Bristol’s School of Physiology, Pharmacology and Neuroscience have discovered a new target in the brain that underpins the eliciting of anxiety and fear behaviours such as ‘freezing’ .
For their study, published in the journal eLife, the scientists set out to investigate how the cerebellum – which is known to be connected to brain regions associated with survival networks – influences activity in the periaqueductal grey (PAG). The PAG is involved in regulating pain and responses to threats and stressors, and “lies at the hub of central networks co-ordinating survival mechanisms, including fear-evoked coping responses such as ‘freezing’.”
The scientists pointed out how although current anxiety-reducing drugs may be effective, they are often associated with unwanted side effects. Hence, any new approaches to treating anxiety and other psychological disorders, which they say affect an estimated 264 million people worldwide, would be welcome.
Lead authors of the study, Dr Charlotte Lawrenson and Dr Elena Paci, said, “Until now, little was understood about how the cerebellum modulates neuronal activity in other brain regions, especially those related to fear and anxiety.”
In the study the scientists described how for their investigations they fitted animal models with electrodes to record activity within the brain’s PAG region and “applied a conditioning task, whereby an auditory tone is paired with a small foot shock, eliciting the formation of a ‘fear memory’ and freezing, a behavioural index of fear”. They demonstrated how within the brain’s PAG area, a subset of brain cells increased their responsiveness to the conditioned tone, “consistent with encoding a fear memory”.
The scientists found that by altering cerebellar output during conditioning, the subsequent timing of fear-related neuronal activity in the PAG became less precise and the duration of fear-related freezing behaviour was increased “confirming that cerebellar-periaqueductal grey interactions contribute to fear conditioning processes”. The team also demonstrated how manipulation of a direct cerebellar-PAG pathway caused impairments in fear conditioned freezing and ultrasonic vocalisations.
Dr Charlotte Lawrenson and Dr Elena Paci commented, “Our results show that the cerebellum is part of the brain’s survival network that regulates fear memory processes at multiple timescales and in multiple ways.” They added, “Raising the possibility that dysfunctional interactions in the brain’s cerebellar-survival network may underlie fear-related disorders and comorbidities.”
The authors commented that their study provides evidence that the cerebellum, through its interactions with survival circuits, regulates the “ability of the PAG to encode a fear memory trace with temporal precision” and also regulates the “timing of appropriate patterns of behaviour during fear acquisition and retrieval”, for example, how long ‘freezing’ lasts.
Their findings provided new insights into the way the PAG encodes fear memory, the authors said, and also provided evidence that the cerebellum is an additional key structure that contributes to fear and anxiety networks. They added, “This offers a novel target for treating psychological conditions including post-traumatic stress disorder.”
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Cite this: Dr Rob Hicks MBBS DRCOG MRCGP. Potential New Target for Anxiety-Reducing Drugs Identified – Medscape – Mar 16, 2022.
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Disclosure: Dr Rob Hicks has disclosed no relevant financial relationships
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