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J Subst Abuse Treat. 1993 Mar-Apr;10(2):161-70.

Neurobehavioral mechanisms of nicotine action: role in the initiation and maintenance of tobacco dependence.

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  • 1Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond 23298.

Abstract

Basic neuroscience research conducted over the last quarter century has provided us with much information concerning potential biobehavioral and neuromolecular mechanisms involved in the initiation and maintenance of tobacco dependence. Nicotinic-acetylcholinergic receptors (AChRs), in addition to having a primary locus on cholinergic neurons, appear to be also located on a variety of noncholinergic neurons (presynaptic and/or postsynaptic sites). Nicotine therefore appears to be able to affect a variety of neuronal pathways involved in behavioral reward and arousal processes, which appear paramount to tobacco dependence. Nicotine appears to have several unique properties at the cellular level that allow it to act both as an agonist and as a potential antagonist at select AChRs. Nicotine's ability to act as an agonist appears to be contingent on an action at nAChRs, which initially open a receptor-linked cation channel, eliciting the entrance of CA++ (or other cations) into the cell. Cation entrance into the cell, therefore, may be the cellular transducer of nicotine's behavioral and dependence-producing effects. Subsequent to this initial agonist effect, the nicotinic receptor is believed to undergo a refractory period, via a desensitization process, during which Ca++ is prevented from further entrance into the cell. It is this ability to induce receptor desensitization which seems central to nicotine's ability to act as an antagonist. The duration of nAChR desensitization may also be useful in explaining individual variability to nicotine's behavioral effects and may be related to the induction of acute and/or chronic tolerance in both animals and man. Nicotine-induced desensitization may also be important to relapse in the smoker if conditioned stimuli are able to provoke such mechanisms, which could lead to the need to smoke. Finally, a model is presented to account for individual smoking patterns and level of tobacco dependence which is partially based on the proposed cellular mechanisms of nicotine action and desensitization at the nAChR.

PMID:
8510190
[PubMed - indexed for MEDLINE]
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