Brain damage from tobacco consumption

Smoking permanently affects the brain

19/12/2012

Smoking is one of the leading causes of death worldwide, with around five million deaths per year. In particular, the damage to the respiratory and cardiovascular systems by tobacco consumption has long been known. But Swiss researchers have now found that smoking in the long term leaves traces in the brain.

As a typical side effect of tobacco use are respiratory complaints such as the smoker's cough (chronic obstructive pulmonary disease, COPD) or lung cancer. According to the results of the Swiss researchers, however, there is also something like a smoker's brain. Because the consumption of tobacco permanently affects the glutamate system in the brain, report the scientists around Gregor Hasler of the University Hospital and Polyclinic for Psychiatry of the University of Bern in the journal „Proceedings of the National Academy of Sciences“ (PNAS). The glutamate receptor mGluR5 is much less common in the brains of smokers and ex-smokers, which has a significant effect on brain signal transduction. The researchers also suspect a correlation of these impairments of the glutamate system with the high rate of relapse in the attempt of smoking withdrawal. Perhaps medications that directly interfere with the glutamate system could help smokers quit smoking, Gregor Hasler and colleagues say.

Sustainable changes in the smoker's brain
The scientists of the University of Bern, the ETH Zurich and the University of Zurich measured the concentration of the metabotropic glutamate receptor 5 (mGluR5) in their joint study in the brains of 14 smokers, ex-smokers and non-smokers using positron emission tomography. The glutamate receptor plays an important role in signaling in the brain. The researchers suspect a connection with the difficulties that have around 90 percent of smokers in smoking cessation. So far, it is unclear why of the approximately 75 percent of smokers who try to withdraw, so many do not hold out. Hasler and colleagues believe that nicotine addiction develops as a kind of learning process in which the glutamate system plays a central role. From previous studies in mice, it is known that glutamate has a significant influence in the development of dependencies, such as nicotine and cocaine addiction. The current results of the scientists seem to support this thesis and also provide a possible explanation for the high rate of relapse in smoking cessation.

Smoker with significantly reduced concentration of the glutamate receptor mGluR5
The investigation with the new method of positron emission tomography revealed that the smokers and ex-smokers had a greatly reduced concentration of the glutamate receptor (mGluR5). „We found a significant global reduction in the mGluR5 distribution“ on average, more than 20 percent in the volume ratio of the so-called gray matter in the 14 smokers, report the researchers in the journal „PNAS“. The most pronounced reductions in the mGluR5 concentration had to be demonstrated in comparison to the non-smokers in the area of ​​the bilateral medial orbitofrontal cortex. Here, the smokers showed about 30 percent lower concentration of the glutamate receptor. Decreased mGluR5 levels, according to the researchers were also observed in the ex-smokers. Although they had not smoked for an average of 25 weeks, they showed a 10 to 20 percent reduction in the glutamate receptor. This illustrates the long-lasting effects of smoking on the brain, the scientists emphasize. Overall, the „Change in the glutamate system in smokers in extent and in the local extension far greater than previously thought“, Hasler and colleagues continue.

Impairment of the glutamate system Cause of the high rate of relapse
The reason for the reduction of the glutamate receptor is, according to the researchers, the persistent nicotine intake. The reduction in mGluR5 levels among ex-smokers suggests that their receptors have not fully recovered yet. Apparently, the recovery of the glutamate system takes a long time, with „It is likely that this very slow normalization contributes to the very high rate of relapse among ex-smokers“, write Hasler and colleagues. The lasting effect smoking has on signal transmission in the brain has not been clear so far. The formation of tolerance in the glutamate system with repeated nicotine consumption probably also contribute to the fact that the abstinence from nicotine with withdrawal symptoms, such as internal restlessness, irritability, anxiety or even physical symptoms, such as headaches, may go along.

Medications for the regulation of the glutamate receptor as an aid in smoking withdrawal?
At the current „Development of drugs that affect the mGluR5 protein“, It should be borne in mind that the effect on smokers and ex-smokers may be significantly different from that of nonsmokers. However, such medicines may also have the potential „to reduce the risk of relapse, withdrawal symptoms and other psychological consequences of nicotine use“, write Hasler and colleagues. Two of the participating researchers work for the pharmaceutical company Novartis, which is currently testing several drugs targeting the mGlu5 receptor. (Fp)

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