Weill Cornell Medicine investigators have identified in a preclinical model a specific brain circuit whose inhibition appears to reduce anxiety without side effects. Their work suggests a new target for treating anxiety disorders and related conditions and demonstrates a general strategy, based on a method called photopharmacology, for mapping drug effects on the brain.
In their study, published Jan. 28 in Neuron, the researchers examined the effects of experimental drug compounds that activate a type of brain-cell receptor called the metabotropic glutamate receptor 2 (mGluR2). While these receptors are found on neurons within many brain circuits, the team showed that activating them in a specific circuit terminating in an emotion-related brain region called the amygdala reduces signs of anxiety without apparent adverse side effects. Current treatments for anxiety disorders, panic disorder and associated conditions can have unwanted side effects including cognitive impairments.
Our findings indicate a new and important target for the treatment of anxiety-related disorders and show that our photopharmacology-based approach holds promise more broadly as a way to precisely reverse-engineer how therapeutics work in the brain.”
Dr. Joshua Levitz, study senior author, associate professor of biochemistry at Weill Cornell Medicine
The co-first authors of the study are Drs. Hermany Munguba and Ipsit Srivastava, a former and current postdoctoral associate, respectively, in the Levitz lab, and Dr. Vanessa Gutzeit, a doctoral student in the Levitz lab at the time of the study.
Activating mGluR2-a tiny “dimmer switch” that reduces the synaptic transmission of its host neuron-