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首页> 外文期刊>The European Journal of Neuroscience >Deletion of alpha 5 nicotine receptor subunits abolishes nicotinic aversive motivational effects in a manner that phenocopies dopamine receptor antagonism
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Deletion of alpha 5 nicotine receptor subunits abolishes nicotinic aversive motivational effects in a manner that phenocopies dopamine receptor antagonism

机译：α5尼古丁受体亚基的缺失以诸着诸着诸多多巴胺受体拮抗作用的方式消除了烟碱的厌恶诱导效应

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摘要

Nicotine addiction is a worldwide epidemic that claims millions of lives each year. Genetic deletion of 5 nicotinic acetylcholine receptor (nAChR) subunits has been associated with increased nicotine intake, however, it remains unclear whether acute nicotine is less aversive or more rewarding, and whether mice lacking the 5 nAChR subunit can experience withdrawal from chronic nicotine. We used place conditioning and conditioned taste avoidance paradigms to examine the effect of 5 subunit-containing nAChR deletion (5 -/-) on conditioned approach and avoidance behaviour in nondependent and nicotine-dependent and -withdrawn mice, and compared these motivational effects with those elicited after dopamine receptor antagonism. We show that nondependent 5 -/- mice find low, non-motivational doses of nicotine rewarding, and do not show an aversive conditioned response or taste avoidance to higher aversive doses of nicotine. Furthermore, nicotine-dependent 5 -/- mice do not show a conditioned aversive motivational response to withdrawal from chronic nicotine, although they continue to exhibit a somatic withdrawal syndrome. These effects phenocopy those observed after dopamine receptor antagonism, but are not additive, suggesting that 5 nAChR subunits act in the same pathway as dopamine and are critical for the experience of nicotine's aversive, but not rewarding motivational effects in both a nondependent and nicotine-dependent and -withdrawn motivational state. Genetic deletion of 5 nAChR subunits leads to a behavioural phenotype that exactly matches that observed after antagonizing dopamine receptors, thus we suggest that modulation of nicotinic receptors containing 5 subunits may modify dopaminergic signalling, suggesting novel therapeutic treatments for smoking cessation.
机译：尼古丁成瘾是全球疫情，每年索取数百万生命。遗传缺失5个烟碱乙酰胆碱受体（NACHR）亚基与尼古丁摄入量增加有关，然而，尚不清楚急性尼古丁是否较少厌恶或更有价值，以及缺乏5个NACHR亚基的小鼠是否可以从慢性尼古丁撤离。我们使用置位调节和调节味道避免范式来检查含有5个亚基的NACHR缺失（5 - ）对Nicotine依赖和 - 依赖于尼古丁依赖和 - 助长小鼠的条件方法和避免行为的影响，并将这些激励效应与那些相比进行了比较在多巴胺受体拮抗作用后引发。我们表明，无依赖的5 - / - 小鼠发现低，非诱导剂量的尼古丁奖励，并且没有显示出厌恶条件的反应或避免对较高的厌恶剂量的尼古丁。此外，尼古丁依赖性的5 - / - 小鼠没有显示出从慢性尼古丁戒断的条件厌恶促进响应，尽管它们继续表现出躯体戒断综合征。这些效果对多巴胺受体拮抗作用但不是添加剂，表明5种NACHR亚基在与多巴胺相同的途径中作用，对尼古丁的厌恶的经验至关重要，但在尼古丁的经验中，而不是依赖于无依赖和尼古丁的刺激作用和 - 举起的动机状态。 5个NACHR亚基的遗传缺失导致行为表型，其与在拮抗多巴胺受体后观察到的行为表型，因此我们建议含有5个亚基的烟碱受体的调节可以改性多巴胺能信号传导，表明吸烟的新型治疗治疗方法。

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