Previously rejected mechanism could unlock clues to nicotine dependence

Cigarette smoke
The University of Michigan researchers hope their findings will spur others to examine the role of microRNAs and the genetic coding process in nicotine dependence.

A biological mechanism previously dismissed as unimportant could explain why quitting smoking is so difficult. This process, a University of Michigan team found, plays a role in the formation of receptor proteins, which govern dependence and withdrawal responses.

Most nicotine research looks at how these receptor proteins, called nicotine acetylcholine receptors, affect dependence. Led by Shawn Xu, the Michigan researchers used roundworm models to focus on a part of the genetic coding process that turned out to boost the production of these receptors. MicroRNAs, which fine-tune gene expression, play a key role in modulating the nicotine withdrawal response, they said. 

"We're seeing a clear link between nicotine, microRNA, the receptor proteins and nicotine-dependent behavior," said Jianke Gong, a researcher in Xu's lab and a lead author of the study, which appears in Cell Reports.

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Xu’s team had previously shown that roundworms respond to nicotine much like mammals do, and that some of the genes that affect nicotine dependence are the same in roundworms and mammals. He hopes that his findings will inspire other scientists to investigate how microRNAs are involved in nicotine dependence in mammals.

"People believed this question had been settled," Xu said. "But we have better tools now. We, as a field, need to take another look at this mechanism in nicotine addiction."

RELATED: GlaxoSmithKline's nicotine franchise pairs up with smoking cessation app

More people in the U.S. are addicted to nicotine than any other drug, the CDC says. And quitting smoking often requires multiple attempts: Of smokers who try to quit, less than 5% successfully do at any one time, according to a 2010 Surgeon General’s report.

Grand View Research valued the smoking cessation and nicotine de-addiction market at $7 billion in 2015 and predicts it will exceed $21 billion by 2024.

In their new study, the University of Michigan team notes that microRNAs are also known to regulate gene expression in other forms of drug abuse, including cocaine dependence. Further studies are required to better understand the mechanisms by which microRNAs govern addiction to these substances, they believe.

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