The effects of nicotine on neural pathways implicated in depression: a factor in nicotine addiction?

The prevalence of tobacco smoking varies considerably between different groups within the community, tobacco smoking being particularly prevalent in patients with depressive disorder. This review will focus on results, derived from animal studies, which suggest that, in addition to its primary reinforcing properties, nicotine also exerts effects in stressful environments, which may account for its enhanced addictive potential in depressed patients. It focuses on the evidence that depression sensitises patients to the adverse effects of stressful stimuli, and that this can be relieved by drugs that stimulate dopamine release in the forebrain. This mechanism, it is proposed, contributes to the increased craving to smoke in abstinent smokers exposed to such stimuli, because they become conditioned to use this property of nicotine to produce rapid alleviation of the adverse effects of the stress. The review also explores the possibility that chronic exposure to nicotine elicits changes in 5-HT formation and release in the hippocampus which are depressogenic. It is postulated that smokers are protected from the consequences of these changes, while they continue to smoke, by the antidepressant properties of nicotine. However, they contribute to the symptoms of depression experienced by many smokers when they first quit the habit.