New study shows how brain adapts to nicotine exposure
European researchers have shed new light on how the brain adapts to long term nicotine exposure - and how it reacts when the drug is withdrawn. The work, which brought together researchers from the French National Centre for Scientific Research (CNRS) and Sweden's Karolinska Institute, is published online by the Proceedings of the National Academy of Sciences (PNAS). Nicotine causes addiction when it interferes with the brain's reward centres by attaching itself to nicotinic acetylcholine receptors. These receptors are made up of five sub-units, and there are 10 types of sub-unit. All are activated by the neurotransmitter acetylcholine, as well as by nicotine. However, these different types of receptor could have different physiological functions and therefore represent distinct drug targets. Last year the researchers from the CNRS showed that the sub-unit beta2, and possibly also another subunit called alpha7, are involved in the activation of the brain's reward system following the injection of a large dose of nicotine. In this latest research, the scientists wanted to find out what these receptors did when exposed to nicotine in the longer term. Over several weeks, they administered nicotine to mice so that the levels of nicotine in their blood plasma were similar to those found in human smokers; enough to trigger withdrawal symptoms. By comparing normal mice with mice that lacked the beta2 receptor, the researchers revealed how the beta2 and alpha7 receptors work to maintain a balance while the brain is exposed to nicotine for a long time. On the one hand, when exposed to nicotine, the beta2 receptors become desensitised and inactive. However, this is counterbalanced by an adaptation of the neuronal circuits with alpha7 receptors. 'In summary, our data obtained in mice provide evidence for a functional balance between nicotinic receptors subtypes that might also take place in smokers under nicotine exposure,' the researchers write. The results mean researchers developing drugs designed to help smokers quit will have to take into account both of these receptors. The findings also have implications for diseases which involve the nicotinic receptors. 'This is notably the case in schizophrenia,' explains Philippe Faure of the CNRS, one of the authors of the paper. 'People treated for this disease smoke significantly more than the general population and some people believe that this could be a form of self-medication. This phenomenon could be due to the action of a compensatory mechanism linked to the alpha7 receptors.' Other diseases which affect the nicotinic receptors include Alzheimer's, Attention Deficit Hyperactivity Disorder (ADHD) and autism. 'These disease states represent outstanding targets for the chronic actions of novel nicotinic drugs,' the researchers conclude.
Countries
France, Sweden