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Study Led by UTHSC’s Burt Sharp, MD, Published In ACS Pharmacology & Translational Science


A study led by Burt Sharp, MD, Distinguished Professor in the UTHSC Department of Genetics, Genomics and Informatics in the College of Medicine, was recently published in ACS Pharmacology & Translational Science.

The study sought to determine whether compounds called positive allosteric modulators (PAMs) reduce the likelihood of stress-induced smoking relapses in nicotine-addicted individuals.

GABA is an inhibitory neurotransmitter that decreases nerve signaling in the brain. When a person experiences stress, the GABA neurotransmission can decrease, causing some neurons to become hyperactive. Using animal models, Dr. Sharp’s lab found that administering PAM compounds that increase the stimulation of GABAA receptors on certain neurons (basolateral amygdala principal output neurons) lessened the stress response. This made the subjects less likely to self-administer increased levels of nicotine during stressful conditions. If similar effects are confirmed in humans, PAMs could be helpful in alleviating smoking relapses caused by stress, with fewer side effects than GABA administration, the researchers say.

The study was supported by a gift from Karin S. Nielsen at Saniona AB, Denmark, and by partial funding from Lohocla Research, Inc. “We are grateful for the support that has enabled my laboratory to conduct these preclinical studies, which provide a strong rationale for human research to improve the success of quitting smoked tobacco,” Dr. Sharp said.

The study is titled, “Allosteric Modulation of GABAA Receptors in Rat Basolateral Amygdala Blocks Stress-Enhanced Reacquisition of Nicotine Self-Administration.” Read the study in the October issue of ACS Pharmacology & Translational Science: https://pubs.acs.org/doi/10.1021/acsptsci.0c00111

ACS Pharmacology & Translational Science is a publication of the American Chemical Society, one of the world’s largest scientific organizations and a leading source of authoritative scientific information.