NEURAL MECHANISMS UNDERLYING NICOTINE DEPENDENCE

There is little doubt that many habitual smokers find it difficult to quit the habit because they have become addicted to the nicotine prese nt in the smoke. This paper addresses some of the pharmacological mech anisms underlying this addiction and discusses how an understanding of these mechanisms may contribute to the more effective use of nicotine replacement therapy during smoking cessation. It considers critically the evidence that the ''rewarding'' properties of nicotine, which ser ve to reinforce drug-seeking behaviour, are related to stimulation of the mesolimbic dopamine system of the brain. The critique focuses spec ifically on the evidence that many central nicotinic receptors, includ ing those which mediate the effects of the drug on dopamine secretion, are readily desensitized by chronic exposure to agonist and that hypo theses which assume that nicotine inhaled from tobacco smoke invariabl y results in stimulation of the receptors must be treated with caution . Nicotinic receptors in the brain are, however, heterogeneous in natu re with different molecular structures and pharmacologies. It is concl uded that the reinforcing properties of nicotine sought by smokers may reflect both stimulation and desensitization of the different nicotin ic receptor populations, and that smokers may adjust their smoking hab its to achieve the balance of receptor stimulation and desensitization which they find most reinforcing. It seems likely that the efficacy o f the different nicotine formulations during the treatment of smoking cessation may also reflect their ability to stimulate or desensitize b rain nicotinic receptors.