Miyata_1998_Nihon.Arukoru.Yakubutsu.Igakkai.Zasshi_33_557

This article reviews the current studies on the mechanism of nicotine dependence. In the process of nicotine dependence, there are four major determinants: reinforcing effects, tolerance, craving and withdrawal. 1) The positive reinforcing effects of nicotine are important especially for the initiation of nicotine self-administration. These effects are considered to be induced by the ability of nicotine to promote the release of catecholamines, acetylcholine, beta-endorphine, glucocorticoid, and other kinds of hormones. 2) However, tolerance gradually develops to the positive reinforcing effects of nicotine, as nicotine is repeatedly self-administered. 3) Craving is defined as the uncontrollability of the urge to take drugs, which is a core aspect of recent ICD-10 or DSM-IV descriptions. Craving for nicotine is caused and enhanced by the following three factors; psychic withdrawal symptoms such as anxiety, depression and dysphoria, conditioning processes leading to the association of nicotine effects with environmental stimuli, and memory of the reinforcing effects of nicotine. 4) Neither somatic withdrawal symptoms nor mental disorders related to nicotine dependence is significant. 5) As for the neurobiology of nicotine dependence, the reward system is focused as a putative responsible region involved not only in the reinforcing effects of nicotine but also in the psychic withdrawal symptoms. The amygdala-nucleus accumbens connection may be intimately involved in the association between nicotine effects and environmental stimuli. And neuronal circuits involved in memory function may be implicated in the manifestation of craving and relapse, but the details remain to be solved.