Home Neuroscience August 17, 2018

Scientists have used a gene-editing tool to target the natural mood-boosting receptors in the brain, an advance that may help alleviate depression in patients who don't find relief with existing drugs.

Most antidepressant drugs target serotonin receptors, aiming to boost serotonin, a chemical thought to regulate mood and social behaviour.

Researchers at Washington University in the US used CRISPR technology to target an altogether different type of receptor called delta-type GABA receptors.

They think that natural mood-boosting substances in the brain can target these receptors.

"There's a real need to develop more effective antidepressants," said Steven Mennerick, principal investigator of the research published in The Journal of Neuroscience.

 

"The most commonly prescribed antidepressant drugs -- such as Prozac, Paxil and Zoloft -- were approved by the FDA more than 30 years ago, and there's been a dearth of new antidepressants since then. A completely new approach is warranted," said Mennerick.

The approach involves targeting GABA receptors with substances called neurosteroids, chemicals that occur naturally in the brain and are involved in emotional and motivational brain networks.

"Neurosteroids are thought to selectively interact with delta-type receptors, and there's evidence that those drugs may help patients suffering from depression," said Mennerick.

Researchers focused on GABA receptors located on neurons in the brain's hippocampus, a part of the brain involved in learning and memory. Using CRISPR, they mutated the delta-type GABA receptors to isolate and test their role in brain functioning.

Earlier studies suggested that targeting these receptors could alleviate symptoms of depression in women suffering from severe postpartum depression.

Mennerick explained that if further studies confirm that activating delta-type receptors has antidepressant effects, a next step would be to develop and test more compounds that activate those receptors.