Cellular and synaptic mechanisms of nicotine addiction

ABSTRACT: The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phe-nomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco al-kaloid with nicotinic acetylcholine receptors (nAChRs). This interaction leads to activation of reward centers in the CNS, including the mesoaccumbens DA system, which ultimately leads to behavioral reinforcement and addiction. Recent findings from a number of laborato-ries have provided new insights into the biologic pro-cesses that contribute to nicotine self-administration. Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure. The high nicotine sensitivity of some nAChR subtypes leads to rapid activation followed in many cases by rapid desensitization. Assessing the rela-tive importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting chal-lenge for future research efforts. © 2002 Wiley Periodicals