Brain: how active our reward?

Researchers at the Institut Pasteur associated with the CNRS have deciphered, in collaboration with the Karolinska Institute in Stockholm (Sweden), the molecular basis of the activation of our reward system, a system that plays a central role in the phenomena of dependence drugs. Their work is published in the journal "Neuron".

Dopaminergic neurons in a brain area defined bine called ventral tegmental area (VTA), are fundamental in enabling our reward system that naturally manages our desires, our pleasures and emotions but also plays a central role in the introduction of drug addiction phenomena.

The team of Philippe Faure, unity Receptors and Cognition of Inserm directed by Jean-Pierre Changeux, associated with the CNRS, in collaboration with the Department of Physiology and Pharmacology, Karolinska Institute in Stockholm, have deciphered the role of nicotinic acetylcholine receptors in the control of this system.

There are ten types of nicotinic receptors, the beta2 types. They are both activated by an endogenous neurotransmitter acetylcholine and nicotine. Jean-Pierre Changeux and his colleagues have been studying for many years the role of these receptors not only in the acquisition of tobacco dependence, but also in various cognitive functions. Each of these types of receptors may have a specific physiological function, and thus constitute a distinct pharmacological target.

When a cigarette is smoked, nicotine stimulates nicotinic receptors on dopaminergic neurons of the VTA, resulting in an increase in the activity of these neurons and the feeling of pleasure associated. This sensation is related to specific activation profiles of dopaminergic neurons.

The researchers have shown that this response to nicotine is due to a type of nicotinic receptor, the beta2 types. They also show that apart from the presence of nicotine and by the action of endogenous acetylcholine, these receptors increase the occurrence of these specific profiles. They participate in the daily management of our emotions and our pleasures.

This study is based on comparative experiments between normal mice and mice lacking ß2 or another type of nicotinic receptors. It shows that the dopamine system is highly reactive in the absence of beta2 receptors, and it is enough to restore locally in ATV these receptors (gene transfer) for the activation of dopaminergic neurons is restored. Other nicotinic receptors, in turn, are not as prominent in the control, but appear to modulate the response once it is established.

Thus detailing the modulation of dopamine system through the "cholinergic system," the Franco-Swedish researchers emphasize the value of beta2 receptor as a drug target not only in the treatment of nicotine addiction but also in other diseases which could be related to a defect in the activity of brain dopamine neurons target the AVT as hyperactivity syndrome ADHD (Attention Deficit Hyperactivity Disorder).

Teams, having highlighted the endogenous mechanisms involved in the ATC, continue to explore the effects of nicotine in this crucial area of drug dependence.