Now Researchers at Washington University School of Medicine in St. Louis and Sage Therapeutics in Boston are trying a different approach to alleviate depression.
Most antidepressant drugs target serotonin receptors, aiming to boost serotonin, a chemical thought to regulate mood and social behavior. Using CRISPR technology, the scientists have been able 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.
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.
That new 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.
There is an “alphabet soup” of GABA receptor subtypes on brain cells. Targeting the delta-type GABA receptor could help alleviate depression because GABA, an inhibitory neurotransmitter, may help slow down some of the cognitive processes that lead to overwhelming and negative thoughts and feelings.
Some types of GABA receptors have been linked to anxiety, but although many scientists have looked at the receptors as potential targets for depression, developing compounds that selectively bind to specific types of GABA receptors has complicated the search.
In new, 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.
If brexanolone works in postpartum depression mainly through these delta-type receptors, then it may work in other types of depression, too. Eventually, the goal would be to develop ever more potent and selective drugs to interact with those same delta-type receptors.
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News Source: https://source.wustl.edu/2018/08/new-approach-to-developing-antidepressants/
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