CHICAGO, Aug. 18 (Xinhua) -- While most antidepressant drugs target serotonin receptors, aiming to boost serotonin, researchers at Washington University School of Medicine in St. Louis and Sage Therapeutics in Boston are trying to target an altogether different type of receptor called delta-type GABA receptors.
The new approach targets GABA receptors with substances called neurosteroids, chemicals that occur naturally in the brain and are involved in emotional and motivational brain networks.
In the study, the 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. The study of 21 women showed that depression improved significantly in those given the drug.
"The drugs affect GABA receptors, but they also seem to have anti-inflammatory properties," said principal investigator Steven Mennerick, a professor of psychiatry at the university. "We think it may be that special mix of reducing inflammation while activating these receptors that contributes to antidepressant effects."
In the next step, the researchers plan to measure the actions of neurosteroids on various GABA receptor subtypes.
"It's very difficult to differentiate among different types of GABA receptors because they share so many common properties," said first author Min-Yu Sun, a postdoctoral researcher in Mennerick's lab.
If further studies confirm that activating delta-type receptors has antidepressant effects, the researchers would test more compounds that activate those receptors.
"We have a catalogue of neurosteroid compounds that our colleagues have been developing over the last 20 years, and any one of them could prove to be an effective antidepressant," Mennerick said. "Eventually, the goal would be to develop ever more potent and selective drugs to interact with those same delta-type receptors."
The study has been published online in the Journal of Neuroscience.
