不含尼古丁的烟草成分的滥用可能性:乙醛、去甲烟碱、可替宁、新烟碱
2012/11/19
摘要
简介:本文对评价乙醛、去甲烟碱、可替宁和新烟碱滥用可能性的现有动物研究进行综述。研究内容包括这些成分对中脑多巴胺(DA)水平影响、药物辨别试验和已知滥用药物的替代品、条件性位置研究、自行给药行为和躯体撤药症状。
结果:乙醛对中脑DA水平和药物辨别存在不同影响,然而都会产生条件性位置偏爱和支持自行给药。有关撤药的单变量研究显示,终止给予乙醛,可导致躯体撤药症状。去甲烟碱可增加中脑(特别是伏核)DA水平。虽然没有条件性位置研究的相关数据,去甲烟碱在药物辨别试验中能替代可替宁,部分替代可卡因和安非他明,并在一项研究支持自行给药。新烟碱能增加中脑DA水平,药物辨别试验中能部分替代尼古丁。可替宁能增加中脑DA水平,替代尼古丁。
结论:乙醛和去甲烟碱存在滥用可能性,新烟碱也具有较大的滥用可能性。虽然现有一些可替宁的研究数据,但不足以说明其存在滥用可能性。有必要进一步研究小生物碱在烟草依赖中的作用。
(林江涛 审校)
Nicotine Tob Res. 2012 Sep 18. [Epub ahead of print]
Abuse Potential of Non-Nicotine Tobacco Smoke Components: Acetaldehyde, Nornicotine, Cotinine, and Anabasine.
Hoffman AC, Evans SE.
Source
Corresponding Author: Allison C. Hoffman, Ph.D., U.S. Food and Drug Administration, Rockville, MD 20850, USA. Telephone: 301-796-9203; Fax: 240-276-3655; E-mail: allison.hoffman@fda.hhs.gov.
Abstract
INTRODUCTION: This review identified published animal studies evaluating the possible abuse potential of acetaldehyde, nornicotine, cotinine, and anabasine based on five commonly used paradigms. These include their effects on midbrain dopamine (DA) levels, drug discrimination and substitution for known drugs of abuse, place conditioning, self-administration behavior, and somatic withdrawal symptoms.
RESULTS: Acetaldehyde had mixed effects on midbrain DA levels and drug discrimination; however, it consistently produced a conditioned place preference and supported self-administration. The single available study on withdrawal found that cessation of acetaldehyde administration resulted in a somatic withdrawal syndrome. Nornicotine increased DA in the midbrain, especially in the nucleus accumbens. Although there are no data on place conditioning, it substituted for nicotine in drug discrimination testing, partially substituted for cocaine and amphetamine, and, though only a single study, supported self-administration. Anabasine increased midbrain DA levels and that it partially substituted for nicotine in drug discrimination testing. Cotinine increased midbrain DA levels and substituted for nicotine.
CONCLUSIONS: The existing literature suggests that acetaldehyde and nornicotine likely possess abuse potential, with anabasine having possible abuse potential. Although some cotinine data were available, it was insufficient to draw conclusions about possible abuse potential. Further research is needed to determine the role of minor alkaloids on tobacco dependence.
Nicotine Tob Res. 2012 Sep 18. [Epub ahead of print]
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