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首页> 外文期刊>Alcoholism: Clinical and experimental research >alpha4beta2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response.
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alpha4beta2* Nicotinic Acetylcholine Receptors Modulate the Effects of Ethanol and Nicotine on the Acoustic Startle Response.

机译：alpha4beta2 *烟碱乙酰胆碱受体调节乙醇和尼古丁对声音惊吓反应的影响。

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SUMMARY: BACKGROUND Ethanol modulates the functional activity of alpha4beta2 neuronal nicotinic cholinergic receptors (nAChR) when measured in vitro, but the potential role of alpha4beta2 nAChRs in regulating behavioral effects of ethanol is unknown. Recently, Tritto et al. (Tritto T, Stitzel JA, Marks MJ, Romm E, Collins AC (2002) Variability in response to nicotine in the LSxSS RI strains: potential role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes. Pharmacogenetics 12:197-208) reported that a polymorphism (A529T) in the alpha4 nAChR subunit gene is associated with variability in nicotine's effects on startle in the LSxSS recombinant inbred (RI) strains. Ethanol also alters the acoustic startle response. Thus, we evaluated the potential role of alpha4beta2 nAChRs in modulating ethanol's effects on acoustic startle.METHODS The effects of ethanol on acoustic startle were determined in the LSxSS RI strains. In addition, the effects of ethanol and nicotine were also measured in alpha4 gain of function and beta2 null mutant mice. The beta2 mutants do not express the major variant of alpha4 nAChRs, alpha4beta2.RESULTS An association between the alpha4 A529T polymorphism and ethanol's effects on startle was found in the LSxSS RI strains; those strains that express the A529 variant of alpha4 were more sensitive to ethanol-induced depression of startle. The alpha4 gain of function mutants were more sensitive to the effects of both nicotine and ethanol and the beta2 null mutants were less sensitive to both drugs.CONCLUSIONS alpha4beta2-containing nAChRs may play important roles in modulating the effects of both ethanol and nicotine on the acoustic startle response. We suggest that nAChR subunit genes should be evaluated as potential contributors to both alcoholism and tobacco abuse.
机译：摘要：背景技术乙醇在体外测量时可调节alpha4beta2神经元烟碱胆碱能受体（nAChR）的功能活性，但尚不清楚alpha4beta2 nAChRs在调节乙醇行为效应中的潜在作用。最近，Tritto等人。 （Tritto T，Stitzel JA，Marks MJ，Romm E，Collins AC（2002）LSxSS RI菌株对尼古丁的响应变异性：α4和α6烟碱样受体基因多态性的潜在作用。药理学12：197-208） α4nAChR亚基基因中的多态性（A529T）与LSxSS重组近交（RI）菌株中尼古丁对惊吓的影响的变异性有关。乙醇还会改变听觉惊吓反应。因此，我们评估了alpha4beta2 nAChRs在调节乙醇对声惊吓中的潜在作用。方法在LSxSS RI菌株中确定了乙醇对声惊吓的影响。此外，还在功能的alpha4增益小鼠和beta2无效突变小鼠中测量了乙醇和尼古丁的作用。 beta2突变体不表达alpha4 nAChRs的主要变异体alpha4beta2。结果在LSxSS RI菌株中发现了alpha4 A529T多态性与乙醇对惊吓的影响之间的联系。那些表达α529A529变体的菌株对乙醇诱导的惊吓抑郁症更为敏感。功能突变体的α4增益对尼古丁和乙醇均较敏感，而β2无效突变体对两种药物均较不敏感。结论含α4β2的nAChRs在调节乙醇和尼古丁对声学的影响中可能起重要作用惊呆了。我们建议应评估nAChR亚基基因作为酗酒和吸烟的潜在因素。

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