Nicotine-related brain disorders: the neurobiological basis of nicotine dependence

1. This paper was written at a moment when the dependence liability of nicotine, the psychoactive component from tobacco, was the center of a dispute between the tobacco manufacturing companies and the scientific community (Nowak, 1994a-c). Without being comprehensive, it tries to summarize evidence compiled from several disciplines within neuroscience demonstrating that nicotine produces a true psychiatric disease, behaviorally expressed as dependence to the drug (American Psychiatric Association, 1994). Nicotine dependence has a biological substratum defined as "neuroadaptation to nicotine." 2. The first part of the article defines terms such as "abuse," "tolerance," "dependence," and "withdrawal." It discusses clinical and experimental facts at the whole-organism level, showing that animals and humans will seek and self-administer nicotine because of its rewarding properties. 3. The second part discusses the neurobiological basis of neuroadaptation to nicotine. It presents information on neuroanatomical circuits which may be involved in nicotine-related brain disorders, such as the mesocorticolimbic pathway and the basal forebrain-frontal cortex pathway. It also discusses work from several laboratories, including our own, that support the notion of a molecular basis for neuroadaptative changes induced by nicotine in the brain of a chronic smoker. 4. Although still under experimental scrutiny, the hallmark of neuroadaptation to nicotine is up-regulation of nicotinic receptors, possibly due to nicotine-induced desensitization of their function (Marks et al., 1983; Schwartz and Kellar, 1985). A correlation between these plastic changes and the behavioral data obtained from animal and human experiments is still needed to understand dependence to nicotine fully.