Targeting mGlu7 could lead to new anxiety and PTSD treatments

Researchers are exploring a new approach to treating anxiety and post-traumatic stress disorder (PTSD) by targeting the brain’s mGlu7 receptor. Recent data suggests that modulating this receptor with negative allosteric modulators (NAMs) could disrupt the reconsolidation of fear memories.

Targeting Fear Memory Reconsolidation

The research, conducted by scientists at the centre for Psychiatric Neurosciences (CNP, CHUV/UNIL) in Lausanne, Switzerland, focused on the effects of ADX71743, a highly selective mGlu7 NAM. Studies using animal models demonstrated that modulating mGlu7 interfered with the process of fear memory reconsolidation – the brain’s way of restabilizing a recalled fear memory.

Did You Know? Anxiety- and stress-related disorders are among the most prevalent neuropsychiatric conditions globally.

According to Tim Dyer, CEO of Addex Therapeutics, current anxiety treatments often target symptoms and require continuous use, potentially leading to tolerance, dependence and relapse. This new research, focusing on memory reconsolidation, represents a different therapeutic avenue.

How the Research Works

Fear memories are initially encoded in the lateral amygdala, a key area for emotional processing. When recalled, these memories become temporarily unstable and susceptible to modification. The study showed that administering ADX71743, either directly into the lateral amygdala or systemically, disrupted fear memory reconsolidation in rats. This disruption was specific to the recalled memory and occurred within a defined timeframe, significantly reducing the fear response.

Expert Insight: Targeting the reconsolidation of fear memories, rather than simply suppressing symptoms, could potentially lead to more durable and effective treatments for anxiety and PTSD, offering a time-limited intervention that addresses the root of the problem.

Electrophysiological analysis revealed that ADX71743 modulates glutamatergic transmission at synapses crucial for fear learning. The compound increased spontaneous excitatory signaling under baseline conditions and prevented long-term potentiation – a key process in memory formation – under high stimulation. Similar effects were observed in human brain tissue, suggesting potential for translation to human treatments.

Future Possibilities

Addex Therapeutics has developed a substantial library of allosteric modulators targeting metabotropic glutamate receptors. The findings from this research will likely inform the future development of therapies for anxiety, and PTSD. Further research could explore the optimal timing and dosage of mGlu7 NAMs in conjunction with memory recall techniques to maximize therapeutic benefit.

Frequently Asked Questions

What is fear memory reconsolidation?

Fear memory reconsolidation is the process where the brain restabilizes a fear memory after it has been recalled.

What is ADX71743?

ADX71743 is a highly selective mGlu7 NAM (negative allosteric modulator) used in the study to investigate the effects of modulating the mGlu7 receptor.

Where was the research conducted?

The research was conducted by scientists at the centre for Psychiatric Neurosciences (CNP, CHUV/UNIL) in Lausanne, Switzerland.

Could a deeper understanding of fear memory reconsolidation lead to more effective, long-lasting treatments for those struggling with anxiety and PTSD?