Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.
Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.
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DOI：
10.1016/j.pbb.2013.10.020
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发表时间：
2013-12
影响因子：
3.6
通讯作者：
LeSage, Mark G.
中科院分区：
文献类型：
--
作者：
Grebenstein, Patricia;Burroughs, Danielle;Zhang, Yan;LeSage, Mark G.
关键词：
减少烟草制品中的尼古丁含量被FDA认为是一项减少烟草制品成瘾性的政策。了解个体对尼古丁减少反应的差异对于制定安全有效的政策至关重要。动物和人类研究表明，尼古丁的强化效应存在性别差异，这表明男性和女性对尼古丁减少政策的反应可能不同。然而，目前还没有研究直接考察尼古丁单位剂量减少对动物尼古丁自我给药（NSA）影响的性别差异。本研究的目的是在啮齿动物自我给药模型中检验这一问题。雄性和雌性大鼠被训练在每天23小时的fr3计划下自我给药尼古丁（0.06 mg/kg）。然后将大鼠暴露于盐水消灭和重新获得NSA，随后每周减少单位剂量（0.03至0.00025 mg/kg），直到达到消灭反应水平。研究人员比较了男性和女性的基线摄入量、对消退的抵抗力、在剂量减少期间反应的代偿性增加程度以及尼古丁的阈值增强单位剂量。我们还进行了指数需求曲线分析，比较男性和女性对尼古丁单价（FR/单位剂量）增加的敏感性（即需求弹性或强化功效）。女性的基线摄入量明显高于男性，代偿量明显低于男性。然而，在强化阈值和需求弹性方面没有性别差异。指数需求函数很好地描述了剂量-反应关系（个体受试者的r2值为> 0.96）。这些发现表明，女性在尼古丁减少政策下可能表现出较少的代偿性吸烟，尽管她们的尼古丁强化阈值和需求弹性可能与男性没有差异。
Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males.
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影响因子：
5.2
作者：
Hatsukami DK;Perkins KA;Lesage MG;Ashley DL;Henningfield JE;Benowitz NL;Backinger CL;Zeller M
通讯作者：
Zeller M
DOI：
10.1158/1055-9965.epi-11-0644
发表时间：
2012-05
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Benowitz NL;Dains KM;Hall SM;Stewart S;Wilson M;Dempsey D;Jacob P 3rd
通讯作者：
Jacob P 3rd
影响因子：
6
作者：
Hatsukami, Dorothy K.;Kotlyar, Michael;Hecht, Stephen S.
通讯作者：
Hecht, Stephen S.
影响因子：
3.4
作者：
CORRIGALL, WA;COEN, KM
通讯作者：
COEN, KM
影响因子：
5.5
作者：
Emery, S;Ake, CF;Kaplan, RM
通讯作者：
Kaplan, RM