French researchers show that the mutation of a gene could explain why some smokers cannot quit smoking, even after several smoking cessations.
Despite your multiple attempts to quit smoking for good, you still cannot quit smoking? The answer behind this impossible dropout may lie in your genes.
In an article published Thursday, October 4 in the scientific journal Current Biology, French researchers from CNRS and Inserm establish a link between nicotine addiction and a mutation present in the CHRNA5 gene, known in the medical world to “code for the a5 subunit of nicotine receptors”. People affected by the mutation of this gene would indeed be more inclined to resume smoking, even after having weaned themselves.
The mutation of the CHRNA5 gene involved
Smokers may well know the toxicity of tobacco and the consequences of its consumption on their health, it is indeed sometimes very difficult for them to quit. Multifactorial, this dependence on cigarettes is explained by the presence of nicotine, a psychoactive substance which acts on the brain by attaching itself to the nicotinic receptors of neurons and the modification of neurotransmitters. These then produce dopamine, a hormone that gives a feeling of well-being and satisfaction.
The more you smoke, the more the brain gets used to the presence of nicotine, and the more sensitive the receptors are: this explains tobacco addiction. When we stop smoking for too long, our body lacks nicotine and a feeling of discomfort appears. This lack can manifest itself in different ways. Nervousness, feverishness, nervousness, anxiety, difficulty concentrating or falling asleep are all signs of withdrawal, which disappear when the brain is once again “supplied” with nicotine.
For Benoît Forget, researcher in the Integrative Neurobiology of Cholinergic Systems Unit (Institut Pasteur / CNRS) and main author of the study, this nicotine addiction can however be reinforced by the mutation of the CHRNA5 gene. “Several studies of human genetics have already shown that this genetic mutation increases the risk of tobacco addiction,” he explains, quoted by 20 minutes. “Based on this premise, we sought to determine which phase of nicotine addiction was affected by the presence of this mutation and what could be its role in the relapse.”
A greater risk of relapse after withdrawal
As part of its research, the team led by Benoît Forget introduced the genetic mutation responsible for tobacco addiction in humans in laboratory rats. The researchers then observed the behavior of the rodents. “We have both observed that this genetic mutation led to a higher consumption of nicotine at high doses, and discovered that it induced a higher proportion of relapse after nicotine withdrawal”, explains the researcher.
It has also emerged during research that these frequent relapses after withdrawal are linked to a “reduction in the activation of neurons in the inter-peduncular nucleus”, a specific area of the brain which contains the majority of the alpha5 subunits of the nicotinic receptors. and which is “composed essentially of inhibitory neurons”. According to Benoît Forget, by reducing the activity of the inter-peduncular nucleus, “the genetic mutation could participate in the activation of other brain structures involved in relapse and therefore lead the weaned smoker to relapse into addiction when he is exposed again to a cigarette “.
This finding could largely explain the nicotine addiction of many smokers. Indeed, says the researcher, 35% of Europeans and 50% of the population of the Middle East are carriers of this genetic mutation.
Towards a more effective targeted therapeutic treatment
For Benoît Forget, this discovery is also decisive for the future of therapeutic smoking cessation because it will allow a very targeted action. “A drug capable of increasing the activity of nicotinic receptors containing the Alpha5 subunit could reduce tobacco consumption and the risk of relapse after withdrawal”, explains Uwe Maskos, head of the Integrative Neurobiology of Systems unit cholinergics (Institut Pasteur / CNRS), co-author of the study.
But once we have made this discovery, what hope does it provide in the fight against tobacco addiction? “By putting your finger on a specific subunit of nicotinic receptors, we can consider therapeutic avenues allowing to imagine a very targeted action”, projects Benoît Forget. These results “suggest that a drug capable of increasing the activity of nicotinic receptors containing the α5 subunit could reduce tobacco consumption and the risk of relapse after withdrawal”, adds Uwe Maskos, head of the unit. of Integrative Neurobiology of Cholinergic Systems (Institut Pasteur / CNRS), co-author of the study.
A new therapeutic target
“If we succeed in developing drugs capable of increasing the activation of neurons in the inter-peduncular nucleus, this could help the brain to better manage the urge to smoke after smoking cessation”, adds Benoît Forget. “Such a drug would thus make it possible to reduce the consumption of nicotine not only in people carrying the genetic mutation, or even in smokers who do not have it, but also to prevent relapse after smoking cessation. all the more interesting given that, by targeting receptors located in certain particular structures of the brain, this therapeutic avenue makes it possible to hope in the long term to obtain a cutting-edge therapeutic effect, very targeted and without too many side effects “.
A hope that Jacques Le Houezec prefers to qualify, tobacco specialist and independent consultant in public health and tobacco dependence. Asked by Slate, he recognizes that the discovery made by the team of French researchers is important, but underlines that “the metabolism of the rat is different from that of the man (like that of the mouse). To express a human gene in the rat for observing these effects is a far cry from human behavior “. He also recalls that we must “take into account the large number of varieties of nicotinic receptors present in the human brain. Without neglecting the secondary reinforcements (affect, behavioral situation, social influences, etc.) which probably play a significant role in smoking relapses “.
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