Gene Mutation May Explain Why Some People Smoke More and Can’t Quit

Gene Mutation May Explain Why Some People Smoke More and Can’t Quit

New research from French scientists shows that some smokers may smoke more and relapse frequently after quitting because of a well-known gene mutation that affects one of the receptors in the brain that react to nicotine.

Nicotinic acetylcholine receptors (aAChRs) are proteins that respond to the neurotransmitter acetylcholine. They also bind with some drugs, including nicotine. When that happens, the receptors activate the reward system in the brain, releasing dopamine, which creates the sensations that make nicotine users desire more of the drug. Each receptor is made up of five “subunits,” which act both in concert and independently.

According to a new study published in the journal Current Biology, a mutation in the CHRNA5 gene that affects one of the nicotinic receptor subunits (the α5 subunit) correlates with a significant increase in risk for nicotine dependence. According to the authors, the mutation is present in about 35 percent of Europeans and up to 50 percent of people in the Middle East.

The researchers implanted the gene mutation in a rat, and compared its effect on behaviors associated with nicotine use and dependence. They discovered that the mutation resulted in higher consumption of nicotine in higher doses. The mutation also caused an increased rate of “nicotine-seeking” behavior after cessation, which explains why many smokers relapse after initially quitting cigarettes.

“This study enabled us to assess the impact of this mutation on various stages of nicotine dependence with a greater degree of accuracy,” lead author Benoit Forget explained. “It provided us with an initial explanation for its mechanism of action, which promotes relapse to nicotine-seeking behavior after smoking cessation.” Benoit is a neurobiologist at the Pasteur Institute in Paris.

The study also showed that the effect of the mutation on nicotine relapse seems to be connected to reduced neuron activity in the part of the brain with the highest concentration of α5 nicotinic receptor subunits. The discovery suggests an opportunity for more effective smoking cessation drugs.

“The results suggest that a drug capable of increasing the activity of nicotinic receptors containing the α5 subunit could reduce tobacco consumption and lower the risk of relapse after cessation,” said Pasteur researcher Uwe Maskos.

Previous research by Dr. Maskos on the same gene mutation showed why sufferers of schizophrenia smoke so much, and how nicotine could be used to help schizophrenic patients. Maskos and his team explained how nicotine “has a direct impact on the restoration of normal activity in nerve cells (neurons) involved in psychiatric disorders such as schizophrenia.”

A great deal of research is being done on nicotine’s cognitive benefits. It has long been known that smokers are less prone to Alzheimer’s and Parkinson’s diseases, which is probably due to nicotine. Current research is exploring the potential of nicotine as a treatment for ADHD and other cognitive problems.