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Worms hooked on nicotine offer clues to addiction

A previously dismissed genetic mechanism may contribute to nicotine dependence and withdrawal, new research suggests.

“We, as a field, need to take another look at this mechanism in nicotine addiction.”

Scientists in the lab of Shawn Xu, a professor in the molecular and integrative physiology department at the University of Michigan Medical School, examined withdrawal responses in the millimeter-long roundworms Caenorhabditis elegans, which get hooked on nicotine just like humans.

The researchers identified specific genes and microRNA that play an essential role in how the roundworms develop nicotine dependence and withdrawal responses—clues that may carry over to the mammalian realm.

The study took a fresh look at a previously dismissed biological mechanism. Most research in the field has focused on how proteins called nicotine acetylcholine receptors contribute to dependence.

Xu and his colleagues focused on an earlier step in the genetic coding process and discovered that a series of genes were involved in a process that ultimately increased the production of the nicotine receptor proteins, with microRNAs—a class of small RNA molecules that help fine-tune gene expression—playing a pivotal role.

“We’re seeing a clear link between nicotine, microRNA, the receptor proteins, and nicotine-dependent behavior,” says Jianke Gong, a researcher in Xu’s lab and one of the lead authors on the study.

Scientists had dismissed this mechanism as unimportant to nicotine dependence. However, Xu points out, those conclusions were made decades ago, using less sophisticated techniques.

Xu’s lab previously demonstrated that the worms exhibit behavioral responses to nicotine similar to what mammals experience, and that some of the genes involved in nicotine dependence in worms are conserved in mammals—meaning the worms are a good genetic and behavioral model for studying nicotine dependence.

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Xu hopes that this latest discovery in C. elegans will now lead other scientists to re-examine the role of these microRNAs in nicotine dependence in mammals, and ultimately lead to a better understanding of what causes the dependence.

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

The researchers report their findings in Cell Reports.

The Marie Skłodowska-Curie Actions Research Fellowship Programme and the National Institutes of Health supported the research. Additional study authors are from University of Michigan and the Huazhong University of and Technology in Science China.

Source: Emily Kagey for University of Michigan

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