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PNU-120596，一种 α7 烟碱型乙酰胆碱受体的正变构调节剂，可逆转雌性大鼠注意定势转换任务中慢性低剂量苯环己哌啶诱导的认知缺陷。

PNU-120596, a positive allosteric modulator of α7 nicotinic acetylcholine receptors, reverses a sub-chronic phencyclidine-induced cognitive deficit in the attentional set-shifting task in female rats.

机构信息

Bradford School of Pharmacy, University of Bradford, Bradford, UK.

出版信息

J Psychopharmacol. 2012 Sep;26(9):1265-70. doi: 10.1177/0269881111431747. Epub 2011 Dec 18.

DOI:10.1177/0269881111431747
PMID:22182741
Abstract

The α7 nicotinic acetylcholine receptors (nAChRs) have been highlighted as a target for cognitive enhancement in schizophrenia. Adult female hooded Lister rats received sub-chronic phencyclidine (PCP) (2 mg/kg) or vehicle i.p. twice daily for 7 days, followed by 7 days' washout. PCP-treated rats then received PNU-120596 (10 mg/kg; s.c.) or saline and were tested in the attentional set-shifting task. Sub-chronic PCP produced a significant cognitive deficit in the extra-dimensional shift (EDS) phase of the task (p < 0.001, compared with vehicle). PNU-120596 significantly improved performance of PCP-treated rats in the EDS phase of the attentional set-shifting task (p < 0.001). In conclusion, these data demonstrate that PNU-120596 improves cognitive dysfunction in our animal model of cognitive dysfunction in schizophrenia, most likely via modulation of α7 nACh receptors.

摘要

α7 型烟碱型乙酰胆碱受体 (nAChRs) 已被确定为精神分裂症认知增强的靶点。成年雌性 hooded Lister 大鼠接受亚慢性苯环己哌啶 (PCP)（2 mg/kg）或载体腹腔内注射，每天两次，共 7 天，然后进行 7 天的清洗。PCP 处理的大鼠随后接受 PNU-120596（10 mg/kg；皮下注射）或生理盐水，并在注意力转换任务中进行测试。亚慢性 PCP 在任务的外维度转换 (EDS) 阶段产生了明显的认知缺陷（p < 0.001，与载体相比）。PNU-120596 显著改善了 PCP 处理大鼠在注意力转换任务的 EDS 阶段的表现（p < 0.001）。总之，这些数据表明 PNU-120596 改善了我们的精神分裂症认知功能障碍动物模型中的认知功能障碍，这很可能是通过调节 α7 nACh 受体实现的。

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