Abstract：
:Tobacco use is estimated to be the largest single cause of premature death in the world. Nicotine is the major addictive substance in tobacco products. After cigarette smoking, nicotine quickly acts on its target, nicotinic acetylcholine receptors (nAChRs), which are widely distributed throughout the mammalian central nervous system and are expressed as diverse subtypes on cell bodies, dendrites and/or nerve terminals. Through the nAChRs in brain reward circuits, nicotine alters dopaminergic (DA) neuronal function in the ventral tegmental area (VTA) and increases dopamine release from VTA to nuclear accumbens (NA), which leads to nicotine reward, tolerance and dependence. After quitting smoking, smokers experience withdrawal symptoms, including depression, irritability, difficulty concentrating or sleeping, headache, and tiredness. Recently, evidence has been accumulated to reveal the molecular and cellular mechanisms of nicotine reward, tolerance and dependence. The outcomes of these investigations provide pharmacological basis for smoking cessation. Here, I briefly summarize recent advancements of our understanding of nicotine reward, tolerance and dependence. Based on these understandings, I propose a double target hypothesis, in which nAChRs and dopamine release process are two important targets for smoking cessation. Dysfunction of nAChRs (antagonism or desensitization) is crucial to abolish nicotine dependence and the maintenance of an appropriate level of extracellular dopamine eliminates nicotine withdrawal syndromes. Therefore, the medications simultaneously act on these two targets should have the desired effect for smoking cessation. I discuss how to use this double target concept to interpret recent therapies and to develop new candidate compounds for smoking cessation.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Wu Jdoi
10.1038/aps.2010.137subject
Has Abstractpub_date
2010-09-01 00:00:00pages
1015-8issue
9eissn
1671-4083issn
1745-7254pii
aps2010137journal_volume
31pub_type
杂志文章abstract：AIM:To develop a novel, in situ gel system for nasal delivery of scopolamine hydrobromide (SCOP) and study its efficacy on motion sickness. METHODS:SCOP in situ gels at 0.2%, 0.5%, and 1.0% gellan gum concentration (w/v) were prepared, respectively, and characterized in terms of viscosity, in vitro release, and nasal ...
journal_title：Acta pharmacologica Sinica
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abstract：AIM:Previous study has shown that endometrial cancers with LKB1 inactivation are highly responsive to mTOR inhibitors. In this study we examined the effect of LKB1 gene status on mTOR inhibitor responses in non-small cell lung cancer (NSCLC) cells. METHODS:Lung cancer cell lines Calu-1, H460, H1299, H1792, and A549 we...
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
doi：10.1111/j.1745-7254.2008.00822.x
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doi：
更新日期：2004-03-01 00:00:00
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pub_type： 杂志文章
doi：
更新日期：2002-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2015-11-01 00:00:00
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pub_type： 杂志文章
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doi：10.1111/j.1745-7254.2007.00536.x
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更新日期：2004-06-01 00:00:00
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doi：10.1111/j.1745-7254.2006.00374.x
更新日期：2006-09-01 00:00:00
abstract：:Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), a rapidly progressing clonal malignancy of CD4+ T lymphocytes. Exploring the host-HTLV-1 interactions and the molecular mechanisms underlying HTLV-1-mediated tumorigenesis is critical for developing efficien...
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更新日期：2017-08-01 00:00:00
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journal_title：Acta pharmacologica Sinica
pub_type： 杂志文章,评审
doi：10.1038/aps.2013.200
更新日期：2014-05-01 00:00:00
abstract：AIM:To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns. METHODS:In 6 beagles, a basket ca...
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pub_type： 杂志文章
doi：10.1038/aps.2012.96
更新日期：2012-12-01 00:00:00
