强调尼古丁对具有高遗传易感性的小鼠对乙醇引起的运动刺激反应的影响。
Accentuating effects of nicotine on ethanol response in mice with high genetic predisposition to ethanol-induced locomotor stimulation.
机构信息
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, Portland, OR, USA.
出版信息
Drug Alcohol Depend. 2013 Jan 1;127(1-3):108-14. doi: 10.1016/j.drugalcdep.2012.06.015. Epub 2012 Jul 12.
BACKGROUND
Co-morbid use of nicotine-containing tobacco products and alcohol is prevalent in alcohol dependent individuals. Common genetic factors could influence initial sensitivity to the independent or interactive effects of these drugs and play a role in their co-abuse.
METHODS
Locomotor sensitivity to nicotine and ethanol, alone and in combination, was assessed in mice bred for high (FAST) and low (SLOW) sensitivity to the locomotor stimulant effects of ethanol and in an inbred strain of mouse (DBA/2J) that has been shown to have extreme sensitivity to ethanol-induced stimulation in comparison to other strains.
RESULTS
The effects of nicotine and ethanol, alone and in combination, were dependent on genotype. In FAST and DBA/2J mice that show high sensitivity to ethanol-induced stimulation, nicotine accentuated the locomotor stimulant response to ethanol. This effect was not found in SLOW mice that are not stimulated by ethanol alone.
CONCLUSIONS
These data indicate that genes underlying differential sensitivity to the stimulant effects of ethanol alone also influence sensitivity to nicotine in combination with ethanol. Sensitivity to the stimulant effects of nicotine alone does not appear to predict the response to the drug combination, as FAST mice are sensitive to nicotine-induced stimulation, whereas SLOW and DBA/2J mice are not. The combination of nicotine and ethanol may have genotype-dependent effects that could impact co-abuse liability.
背景
在酒精依赖个体中，同时使用含尼古丁的烟草制品和酒精的情况很常见。共同的遗传因素可能会影响对这些药物的独立或交互作用的初始敏感性，并在它们的共同滥用中发挥作用。
方法
在对乙醇的运动刺激作用具有高（FAST）和低（SLOW）敏感性的小鼠中以及在已显示出对乙醇诱导的刺激比其他品系更敏感的近交系小鼠（DBA/2J）中，评估了尼古丁和乙醇单独使用和联合使用对运动敏感性的影响。
结果
尼古丁和乙醇单独和联合的作用取决于基因型。在对乙醇诱导的刺激具有高敏感性的 FAST 和 DBA/2J 小鼠中，尼古丁增强了对乙醇的运动兴奋剂反应。在单独用乙醇不能刺激的 SLOW 小鼠中未发现这种作用。
结论
这些数据表明，单独对乙醇的刺激作用的敏感性的差异的遗传基础也会影响尼古丁与乙醇联合使用时的敏感性。单独对尼古丁的刺激作用的敏感性似乎不能预测药物联合的反应，因为 FAST 小鼠对尼古丁诱导的刺激敏感，而 SLOW 和 DBA/2J 小鼠则不敏感。尼古丁和乙醇的联合可能具有基因型依赖性的影响，可能会影响共同滥用的倾向。
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