Nicotine addiction : a review

Nicotine, the major psychoactive compound in tobacco, acts as a potent addictive drug in humans. The addictive nature of nicotine leads to more than 6 million deaths a year. Evidence indicates that nicotine and other drugs of abuse act on central dopaminergic pathways and modulate their neurophysiological mechanisms. Nicotine stimulates dopaminergic pathways and the prefrontal cortex (PFC), inducing enhanced reward perception and increased cognitive function, respectively. These findings are consistent with the fact that nicotine binds to different subtypes of nicotinic acetylcholine receptors present on the neurons found in the PFC and ventral tegmental area of the midbrain. The latter, being the area most involved in addictive behaviour, projects on the limbic system, particularly the nucleus accumbens, and receives afferents from the prefrontal cortex and brainstem. Although dopaminergic pathways and nicotinic acetylcholine receptors are the protagonists of nicotine addiction, several minor pathways and their constituent receptors have been indicated as being either directly or indirectly affected by nicotine. These include serotonergic pathways and central cannabinoid receptors. Despite the scarcity of approved drugs and partial efficacy of approved treatment, insight into nicotine neurophysiological modulation led to better appreciation of nicotine-seeking behaviour and subsequent improved design of pharmacological and behavioural approaches to smoking cessation. Tobacco is the single most preventable cause of death in the world today. Better understanding of the neurobiological mechanisms underlying nicotine addiction will ultimately lead to more effective treatments of both nicotine dependence and nicotine rewarding effects.