Featured Review Cell Science Reviews Vol 5 No 4 ISSN 1742-8130

Unmasking the role of nicotinic receptors in nicotine addiction:
recent advances in understanding nicotine action on dopamine systems

Nicotine addiction through tobacco smoking is one of the largest single, preventable causes of morbidity and premature mortality worldwide. Yet, we still lack complete knowledge of the neuronal mechanisms underlying nicotine action, and certainly lack definitive treatments for nicotine addiction. Continued research effort is warranted if we are to understand the factors that govern nicotine dependence. The last five years has seen an unprecedented array of methodologies be used to study nicotine action in the central nervous system, including genetic, molecular, electrophysiological, electrochemical, and behavioural approaches. Much effort continues to be directed at elucidating the nicotinic receptors (nAChRs) and mechanisms through which nicotine acts on the mesostriatal dopamine (DA) systems that project from midbrain (ventral tegmental area and substantia nigra) to striatum (ventral, or nucleus accumbens, and dorsal, or caudate-putamen). These systems signal information about innate and learned rewards, as well as learned drug-associated stimuli, or predictive cues, which may motivate drug-seeking. Recent findings have begun to reconcile previously contradictory findings about nicotine action on mesostriatal DA systems and, in particular, have changed our understanding of the roles played by different nAChRs as well as receptor desensitization in nicotine action. These findings have also identified new disparities e.g. between nAChR expression versus function, and have suggested new hypotheses to test. Here, we discuss how recent findings and technologies have challenged our assumptions and informed our thinking about the mechanisms and receptors through which nicotine acts on DA systems and thus ultimately, might be addictive.

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