Nicotinic receptors in relation to nicotine addiction - Target article on nicotine-addiction
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The first step in processing nicotine's effects on the brain is the drug's interaction with neuronal nicotinic receptors (nAChR). The diversity of nAChR subtypes, their various modes of response (activation, desensitisation, prolonged inactivation), and the complex pharmacokinetics of nicotine delivery conspire to make this a complex issue that is difficult to unravel. The alpha4beta2 nAChR subtype has the highest affinity for nicotine and is the primary candidate for mediating nicotine's central effects. Chronic nicotine exposure (in both humans, animals and cell culture systems) leads to an increase in numbers of alpha4beta2 nAChR (upregulation), with functional implications for withdrawal. However, there is little evidence presently that nAChR upregulation is pertinent to the induction or maintenance of dependence. However, the particular characteristics of the alpha7 subtype of nAChR suggest that it may participate in long term changes in synaptic efficacy that could be relevant to nicotine dependence.