某些研究提示，香烟或酒精可以是人们在转向使用大麻或可卡因前用的“诱导性毒品”。
Amir Levine及其同事探索了这一从尼古丁到可卡因的诱导效应的生物学基础并发现，在小鼠的研究中，尼古丁可增强机体对可卡因的反应。
这一对可卡因的改变了的反应只发生在当小鼠用尼古丁进行“预处理”并接着同时接受了尼古丁和可卡因时。
研究人员提示，尼古丁增强了可卡因的袭击能力及增加FosB基因表达的能力，FosB 基因控制着部分的对可卡因的行为反应。
Levine及其同事发现，来自纽约州的一小组高中生的数据与那些在小鼠中的发现有着良好的匹配，对这些高中生进行追踪的年龄为从15岁至34岁。
该组中的大多数的可卡因使用者在他们开始用可卡因之前都吸过烟，并且当他们是活跃的吸烟者的时候开始使用可卡因的。
研究人员写道：“我们的数据提示，有效的干预措施不仅仅可防止吸烟及其对健康的负面影响，而且它还可降低进展成为使用慢性非法药品的风险。” 在一篇相关的《观点栏目》中，国立药物滥用研究所负责人Nora Volkow指出，这些研究结果还可导致新的成瘾性药物的分子靶点的发现。(生物谷 Bioon.com)
doi:10.1126/scitranslmed.3003062
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Molecular Mechanism for a Gateway Drug: Epigenetic Changes Initiated by Nicotine Prime Gene Expression by Cocaine
Amir Levine, YanYou Huang, Bettina Drisaldi, Edmund A. Griffin Jr., Daniela D. Pollak, Shiqin Xu1, Deqi Yin, Christine Schaffran, Denise B. Kandel and Eric R. Kandel
In human populations, cigarettes and alcohol generally serve as gateway drugs, which people use first before progressing to marijuana, cocaine, or other illicit substances. To understand the biological basis of the gateway sequence of drug use, we developed an animal model in mice and used it to study the effects of nicotine on subsequent responses to cocaine. We found that pretreatment of mice with nicotine increased the response to cocaine, as assessed by addiction-related behaviors and synaptic plasticity in the striatum, a brain region critical for addiction-related reward. Locomotor sensitization was increased by 98%, conditioned place preference was increased by 78%, and cocaine-induced reduction in long-term potentiation (LTP) was enhanced by 24%. The responses to cocaine were altered only when nicotine was administered first, and nicotine and cocaine were then administered concurrently. Reversing the order of drug administration was ineffective; cocaine had no effect on nicotine-induced behaviors and synaptic plasticity. Nicotine primed the response to cocaine by enhancing its ability to induce transcriptional activation of the FosB gene through inhibition of histone deacetylase, which caused global histone acetylation in the striatum. We tested this conclusion further and found that a histone deacetylase inhibitor simulated the actions of nicotine by priming the response to cocaine and enhancing FosB gene expression and LTP depression in the nucleus accumbens. Conversely, in a genetic mouse model characterized by reduced histone acetylation, the effects of cocaine on LTP were diminished. We achieved a similar effect by infusing a low dose of theophylline, an activator of histone deacetylase, into the nucleus accumbens. These results from mice prompted an analysis of epidemiological data, which indicated that most cocaine users initiate cocaine use after the onset of smoking and while actively still smoking, and that initiating cocaine use after smoking increases the risk of becoming dependent on cocaine, consistent with our data from mice. If our findings in mice apply to humans, a decrease in smoking rates in young people would be expected to lead to a decrease in cocaine addiction.
