TY - JOUR
T1 - Molecular mechanisms of nicotine dependence
AU - Ortells, Marcelo O.
AU - Arias, Hugo R.
N1 - Funding Information:
This review was supported by grants from the CONICET, Argentina (to M.O.O.), and from the Science Foundation Arizona and Stardust Foundation and the College of Pharmacy, Midwestern University (to H.R.A.).
Publisher Copyright:
© 2010-IOS Press and the authors. All rights reserved.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Nicotine is the main psychoactive substance present in tobacco, targeting neuronal nicotinic acetylcholine receptors (AChRs). The main effects of nicotine associated with smoking are AChR activation, desensitization, and upregulation, with the subsequent modulation of the mesocorticolimbic dopaminergic system. However, there is a lack of a comprehensive explanation of their roles that effectively makes clear how nicotine dependence might be established on those grounds. Receptor upregulation is an unusual effect for a drug of abuse, because theoretically this implies less need for drug consumption. Receptor upregulation and receptor desensitization are commonly viewed as opposite, homeostatic mechanisms. We here review the available information on smoking addiction, and drugs employed as aids in smoking cessation, especially under a recently presented model of nicotine dependence. In this model both receptor upregulation and receptor desensitization are responsible for establishing a biochemical mechanism of nicotine dependence, which have an important role in starting and maintaining tobacco addiction. Basically, a conclusion of this model is that those drugs used for smoking cessation should inhibit preferentially α4β2-containing AChRs and to have a low or null ability to upregulate AChRs, as this characteristic allows the smoker to achieve downregulation without abstinence symptoms.
AB - Nicotine is the main psychoactive substance present in tobacco, targeting neuronal nicotinic acetylcholine receptors (AChRs). The main effects of nicotine associated with smoking are AChR activation, desensitization, and upregulation, with the subsequent modulation of the mesocorticolimbic dopaminergic system. However, there is a lack of a comprehensive explanation of their roles that effectively makes clear how nicotine dependence might be established on those grounds. Receptor upregulation is an unusual effect for a drug of abuse, because theoretically this implies less need for drug consumption. Receptor upregulation and receptor desensitization are commonly viewed as opposite, homeostatic mechanisms. We here review the available information on smoking addiction, and drugs employed as aids in smoking cessation, especially under a recently presented model of nicotine dependence. In this model both receptor upregulation and receptor desensitization are responsible for establishing a biochemical mechanism of nicotine dependence, which have an important role in starting and maintaining tobacco addiction. Basically, a conclusion of this model is that those drugs used for smoking cessation should inhibit preferentially α4β2-containing AChRs and to have a low or null ability to upregulate AChRs, as this characteristic allows the smoker to achieve downregulation without abstinence symptoms.
KW - AChR desensitization
KW - AChR upregulation
KW - neurotransmitter release
KW - nicotine addiction
KW - Nicotinic receptors
UR - http://www.scopus.com/inward/record.url?scp=85021648800&partnerID=8YFLogxK
U2 - 10.1055/s-0036-1586370
DO - 10.1055/s-0036-1586370
M3 - Article
AN - SCOPUS:85021648800
SN - 1879-5390
VL - 1
SP - 75
EP - 89
JO - Journal of Pediatric Biochemistry
JF - Journal of Pediatric Biochemistry
IS - 2
ER -