A novel brain mechanism for nicotine addiction

Researchers from the Hospital del Mar Medical Research Institute (IMIM) in collaboration with scientists from Pompeu Fabra University, the Pasteur Institute and Pierre and Marie Curie University, have discovered a crucial neural mechanism that explains the process of nicotine reward and addiction.

Nicotine, the principal psychoactive component of tobacco, is quickly absorbed through the nasal, oral and respiratory membranes and takes 7 seconds to reach the brain where the receptors are located. It is there where it acts on the central nervous system as well as the autonomic nervous system. This almost immediate relationship between the inhalation of the smoke and its effect at a cerebral level is one of the factors contributing to the highly addictive nature of nicotine. This is explained by the fact that the nicotine exerts its psychopharmacological effects by activating receptors that are very abundant in several specific regions of the brain, the nicotinic acetylcholine receptors (nAChR).

The study has found that some of these cerebral receptors contain a subunit known as beta4. This is present almost exclusively in a key pathway in the brain's reward circuit* and is crucial for the positive reward effects caused by the nicotine in our brain.

“The project, which was carried out using mice, found that those lacking the gene codifying for subunit beta4 showed reduced nicotine consumption and an abnormal neuronal response to nicotine from the dopamine "reward" system. Selectively replacing this nicotine receptor subunit in these mice using a virus, restored the nicotine consumption as well as the dopaminergic response to the nicotine”, explains Patricia Robledo, a researcher in the Integrated Pharmacology and Neuroscience Systems group at the Mar Institute of Medical Research (IMIM) and the coordinator of the study.

“These results confirm studies on human genetic data which postulate that variation in the gene codifying for subunit beta4 can alter the behaviour of smokers and affect individual vulnerability to nicotine addiction”, concludes Patricia Robledo.

The new neurobiological target discovered in this work will help clarify the basis of nicotine addiction, and, therefore, could be useful in the future design of more rational therapeutic plans for quitting smoking.

*the habenulo-interpeduncular pathway

Reference article

Role of β4* Nicotinic Acetylcholine Receptors in the Habenulo-Interpeduncular Pathway in Nicotine Reinforcement in Mice. Harrington L, Viñals X, Herrera-Solís A, Flores A, Morel C, Tolu S, Faure P, Maldonado R, Maskos U, Robledo P. Neuropsychopharmacology. 2015 doi: 10.1038/npp.2015.346. [Epub ahead of print].