Smoking would increase sensitivity to stress

Several clinical trials report a very strong association between mood disorders and addiction to tobacco. Researchers from the Institute of Biology Paris-Seine1 (Neuroscience Paris-Seine) and the Institut de Pharmacologie Moléculaire & Cellulaire (Sophia Antipolis, Valbonne) have investigated the relationship between stress and nicotine, and show that smoking increases sensitivity to stress. This is due to a specific action on α7 nicotinic receptors. These results have been published in Molecular Psychiatry2.

The high comorbidity between smoking and mood disorders would result from a mechanism of mutual maintenance in which each pathology perpetuates the other. However, the mechanisms underlying this relationship remain unknown. Nicotine, tobacco’s main addictive molecule, is a psychoactive substance to which repeated exposure alters the functioning of several neuronal networks. It is generally admitted that a lack of nicotine leads to stress while smoking relaxes. This belief is actually wrong. In the present study, the researchers prove that nicotine exposure increases stress sensitivity, a major risk factor in mood disorders.

The researchers first evaluated the impact of a chronic stress among mice. Mice exposed to repeated attacks by stronger and more agressive congeners indeed show signs of anxiety and a major social aversion. As a result, when exposed to an unknown fellow, whatever its strength and aggressiveness, previously molested mice prefer to avoid any social interaction. Conversely, mice that have not suffered a chronic stress strongly interact with any new individual. Researchers have then observed the following facts. MLA-treated mice, an antagonist of α7 nicotinic receptors, do not show the social avoidance observed after ten days of assault. This suggests that activation of nicotinic receptors is required for the expression of behaviors associated to assaults. . Conversely, activating the α7 receptor amplifies the effect of stress. Finally, researchers have shown that a single attack is not enough to induce signs of social avoidance. However, if a mouse is exposed to nicotine or to a positive allosteric modulator of the α7 receptor, mice develop social avoidance after only one assault.

These findings suggest a direct link between stress and the nicotinic system, which may explain why stress-related diseases are a major risk factor for tobacco addiction . They also show that nicotine exacerbates the effects of acute stress. Nicotine, provided by tobacco smoke, but also by electronic cigarettes, could increase the vulnerability of an individual to develop mood disorders due to stressful events.

This work has been published on the INSB (CNRS) website and also on France Info's website.

1. Team Neurophysiology and behavior

2. Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells’ activity. Morel C*, Fernandez SP*, Pantouli F, Meye FJ, Marti F, Tolu S, Parnaudeau S, Marie H, Tronche F, Maskos U, Moretti M, Gotti C, Han MH, Bailey A, Mameli M, Barik J**, Faure P** (2017) Mol Psychiatry