Nicotine triggers both aversion and pleasure in the brain. The more a person smokes, the more the motivational system changes. By targeting the neurons responsible for nicotine aversion, Canadian researchers hope to develop more effective drugs to quit smoking.
All smokers agree on one point: their first puff of cigarettes was not heavenly. The first contact with tobacco is always disgusting. This instinctive reaction to bitterness (take children and chicory) allowed our ancestors to avoid poisonous plants. And yet, adults return of their own free will to tobacco and eventually become addicted. Canadian researchers have tried to understand the mechanism behind this curious paradox. Their study, published on November 27 in the journal Proceedings of the National Academy of Sciences shows that reward and aversive responses are generated by two different populations of neurons that are found in the same region of the brain, the ventral tegmental area. Ultimately, this better understanding of nicotine addiction could perhaps lead to the development of better therapeutic treatments to quit smoking, they hope.
In order to differentiate between the two populations of nicotine-activating neuronal cells in the ventral tegmental air, researchers at the University of Toronto (Canada) first worked with mice without nicotine receptors. These rodents were therefore at first completely indifferent to nicotine. Then the scientists infected them with a virus to introduce nicotine receptors into the dopaminergic or GABA neurons. They then exposed the animals to nicotine levels corresponding to those of a heavy smoker. They then noticed with surprise that aversion was activated by dopamine neurons while GABA neurons sent the reward signal. A result in opposition to the known theories according to which dopamine is reserved for the circuit of the reward.
However, once the person is addicted, the brain is “trapped” and the motivation system changes. “The aversion (to nicotine, editor’s note) should be there all the time, but the more someone smokes, the more there are going to be changes in the amount of receptors and in the signaling processes in the brain’s reward system. , explains Taryn E. Grieder, lead author of the study. Although dopaminergic neurons are responsible for aversion in non-addicted animals, they signal both reward and aversion once addiction is established., It is no longer about having a pleasant feeling, but about relieving the unpleasant feeling of not having enough drugs”, she continues. Thus, the need to relieve the negative effect of nicotine withdrawal becomes stronger than the instinctive repulsion to nicotine.
Develop a new treatment to facilitate smoking cessation
“Nicotine addiction that results from long-term smoking is a global epidemic. Here we show that nicotinic receptors containing specific subunits, located in the brain’s reward system, mediate the experience of the acute and aversive effects of nicotine, depending on the neurons they contain. These results provide contradictory evidence to the popular belief that the brain dopamine system only mediates the rewarding effects of drug abuse, and instead provide evidence that the aversive motivational effects of nicotine are also signaled by this system. ”, note the researchers in their study.
“Our results lead to a better understanding of the neurobiological substrates of nicotine reward and aversion and may therefore lead to possible new targets for pharmacotherapeutic treatments of tobacco dependence.”
The long-term goal would be to develop a nicotine aversion-enhancing drug, in the style ofAntabusewhich causes nausea and vomiting when alcohol is ingested with it to deter alcoholics from drinking.
Lung cancer, asthma, skin problems, cardiovascular disease, anxiety…
The harmful consequences of tobacco on health are very wide. Smoking is the cause of cardiovascular disease, 16 cancers (especially lung cancer) or one third of all cancer cases. It can lead to 21 chronic diseases, including asthma, diabetes, and erectile dysfunction, to name the most well-known. Smokers are also more likely to develop or worsen psychological problems such as anxiety, depression or nervousness. Finally, tobacco causes the skin to age prematurely and, in addition to reducing the quality of life (sleep disorders, difficult physical exertion), it reduces life expectancy by ten years.
In metropolitan France, in 2015, “75,320 deaths were estimated to be attributable to smoking out of the 580,000 recorded deaths”, announced Public Health France at the end of May. Of these deaths, 61.7% are due to cancer, 22.1% to cardiovascular disease and 16.2% to respiratory disease (16.2%).
“As in most industrialized countries, smoking remains the leading cause of preventable death in France,” noted the organization. However, behaviors are changing since, since 2016, the number of daily tobacco users would have decreased by 1.6 million in France.
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