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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The smoking cessation drug varenicline improves deficient P20-N40 inhibition in DBA/2 mice.
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The smoking cessation drug varenicline improves deficient P20-N40 inhibition in DBA/2 mice.

机译：戒烟药物伐尼克兰可改善DBA / 2小鼠中P20-N40的抑制不足。

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Varenicline, an FDA approved smoking cessation pharmacotherapy, is an alpha4beta2* nicotinic acetylcholine receptor (nAChR) partial agonist and an alpha7* nAChR full agonist. Both subtypes of nAChR are involved in modulating auditory evoked responses in rodents. In DBA/2 mice, an inbred strain, auditory evoked responses to paired auditory stimuli fail to inhibit to the second stimulus. This mouse strain replicates the auditory evoked response inhibition deficit experienced by the majority of schizophrenia patients. In this current study, we examined the effects of five different doses of varenicline (0.06, 0.3, 0.6, 3 and 6mg/kg) on auditory evoked responses in anesthetized DBA/2 mice. We also administered alpha4beta2* and alpha7* nAChR selective antagonists prior to varenicline administration to determine which nAChR subtypes mediate the effects of varenicline. Four of the five doses of varenicline produced improvements in auditory evoked response inhibition deficits. Selective blockade of either the alpha4beta2* or alpha7* nAChR in competition with 0.6mg/kg varenicline prevented varenicline induced improvements. In competition with a higher dose of varenicline (3mg/kg) only blockade of the alpha4beta2* nAChR prevented varenicline induced improvement in auditory evoked response inhibition. These data indicate the importance of alpha4beta2* nAChRs and the potential involvement of the alpha7* subtype in varenicline's effects on auditory evoked responses in DBA/2 mice.
机译：Varenicline是FDA批准的戒烟药物疗法，是alpha4beta2 *烟碱乙酰胆碱受体（nAChR）部分激动剂和alpha7 * nAChR完全激动剂。 nAChR的两个亚型都参与调节啮齿动物的听觉诱发反应。在DBA / 2小鼠中，近交品系对配对听觉刺激的听觉诱发反应不能抑制第二种刺激。该小鼠品系复制了大多数精神分裂症患者经历的听觉诱发反应抑制缺陷。在本研究中，我们检查了五种不同剂量的缬尼克林（0.06、0.3、0.6、3和6mg / kg）对麻醉的DBA / 2小鼠听觉诱发反应的影响。在伐尼克兰给药之前，我们还施用了alpha4beta2 *和alpha7 * nAChR选择性拮抗剂，以确定哪些nAChR亚型介导了伐尼克兰的作用。五种缬草酸中的四种在听觉诱发反应抑制缺陷方面产生了改善。与0.6mg / kg伐尼克兰竞争时，选择性阻断alpha4beta2 *或alpha7 * nAChR阻止了伐尼克兰引起的改善。在与更高剂量的伐尼克兰（3mg / kg）竞争中，仅α4β2* nAChR的阻滞阻止了伐尼克兰在听觉诱发反应抑制方面的改善。这些数据表明alpha4beta2 * nAChRs的重要性，以及alpha7 *亚型可能参与了伐尼克兰对DBA / 2小鼠的听觉诱发反应的影响。

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