Published August 20, 2019
Jun-Xu Li, MD, PhD, has been awarded a five-year, $2 million National Institutes of Health grant to investigate a novel therapy that may prove more powerful than currently available smoking cessation treatments.
Some smoking cessation therapies currently marketed, including nicotine replacement therapy, act directly on nicotinic acetylcholine receptors. But Li says it may also be possible to thwart nicotine’s addiction-related effects through a different mechanism, by indirectly modulating the dopaminergic system, the neurotransmitter system that plays a key role in the reward-motivated behaviors involved in drug addiction.
Li, an associate professor in the Department of Pharmacology and Toxicology, is studying a receptor that has recently emerged as a novel target for treating drug addiction. The receptor is Trace amine associated receptor (TAAR1).
TAAR1, which is expressed in key drug reward and addiction regions of the brain, indirectly modulates the addiction-related effects of nicotine.
Recent research has revealed that mice lacking TAAR1 are more sensitive to potentially addictive behavioral effects of psychostimulants, such as amphetamine. Using recently developed compounds that bind selectively to TAAR1, Li and his colleagues have examined in animal models the effects of treating addictive behaviors with TAAR1.
“Our preliminary data have shown in animal models that treatment with TAAR1 can reduce some of the addiction-related effects of nicotine,” says Li.
“We also found that one of the selective TAAR1 compounds drastically attenuated the rewarding and reinforcing effects of both cocaine and methamphetamine. These findings strongly suggest that they may be potentially effective against psychostimulant abuse and dependence.”
“Our goal now is to systematically assess the therapeutic potential for treating nicotine addiction using chemicals that bind TAAR1 receptors,” he notes.
In previous preclinical research, Li demonstrated that treatment with TAAR1 can severely blunt a broad range of cocaine addiction behaviors.
The findings, reported in the paper “Role of TAAR1 Within the Subregions of the Mesocorticolimbic Dopaminergic System in Cocaine-Seeking Behavior,” were published in the Journal of Neuroscience in January 2017.
Those data led him and his colleagues to consider investigating if TAAR1 would have similar effects on nicotine addiction, emerging as a novel smoking cessation therapy.