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 scientif ic community (Nowak, 1994a-c). Without being comprehensive, it tries t o summarize evidence compiled from several disciplines within neurosci ence 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 d efined as ''neuroadaptation to nicotine.'' 2. The first part of the ar ticle defines terms such as ''abuse,'' ''tolerance,'' ''dependence,'' and ''withdrawal.'' It discusses clinical and experimental facts at th e whole-organism level, showing that animals and humans will seek and self-administer nicotine because of its rewarding properties. 3. The s econd part discusses the neurobiological basis of neuroadaptation to n icotine. It presents information on neuroanatomical circuits which may be involved in nicotine-related brain disorders, such as the mesocort icolimbic pathway and the basal forebrain-frontal cortex pathway. It a lso discusses work from several laboratories, including our own, that support the notion of a molecular basis for neuroadaptive changes indu ced by nicotine in the brain of a chronic smoker. 4. Although still un der experimental scrutiny, the hallmark of neuroadaptation to nicotine is up-regulation of nicotinic receptors, possibly due to nicotine-ind uced desensitization of their function (Marks et al., 1983; Schwartz a nd Kellar, 1985). A correlation between these plastic changes and the behavioral data obtained from animal and human experiments is still ne eded to understand dependence to nicotine fully.