Cellular and synaptic mechanisms of nicotine addiction.
The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid 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 laboratories have provided new insights into the biologic processes 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 relative importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting challenge for future research efforts.
Mansvelder
Huibert D
HD
Vrije Universiteit Amsterdam, Faculty of Earth and Life Sciences, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.
McGehee
Daniel S
DS
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012907:Smoking / Q000503:physiopathology; D013569:Synapses / Q000378:metabolism; D014029:Tobacco Use Disorder / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D011978:Receptors, Nicotinic; D009538:Nicotine; D004298:Dopamine