Tobacco addiction: a biochemical model of nicotine dependence.

Nicotine is the main psychoactive substance present in tobacco, targeting in the CNS the nicotinic acetylcholine receptors (nAChR). The main effects of nicotine associated with smoking are nAChR upregulation, nAChR desensitization and modulation of the dopaminergic system. However, there is a lack of a comprehensive explanation of their roles that effectively makes clear how nicotine dependence might be established on those grounds.

A model for the assembly of nicotinic receptors based on subunit-subunit interactions.

Neuronal ion-channels are complex multimeric proteins. Within a given family, the variability of their pharmacological responses depends on subunit composition and subunit arrangement. We report here that protein assembly in the pentameric nicotinic acetylcholine receptor family, the best characterized of all neuronal receptors, can be predicted using information derived from homology modeled surface to surface subunit interactions based on the atomic structure of a snail acetylcholine-binding protein.