McLean Samantha L, Harte Michael K, Neill Joanna C, Young Andrew Mj
1 School of Pharmacy and Medical Sciences, University of Bradford, Bradford, UK.
2 Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester, UK.
J Psychopharmacol. 2017 Jun;31(6):660-666. doi: 10.1177/0269881117704988. Epub 2017 Apr 26.
Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR).
Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task.
Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p < 0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no PFC dopamine increase was observed.
These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.
前额叶皮质（PFC）中的多巴胺失调在精神分裂症的认知功能障碍中起重要作用。亚慢性苯环利定（scPCP）治疗会导致啮齿动物出现认知障碍，并且是精神分裂症认知缺陷的一种经过充分验证的动物模型。我们研究的目的是调查PFC多巴胺在scPCP诱导的与该疾病相关的认知任务——新物体识别（NOR）缺陷中的作用。
12只成年雌性利斯特戴帽大鼠每天经腹腔注射scPCP（2 mg/kg）或溶剂两次，持续7天，随后有7天的洗脱期。在NOR任务之前、期间和之后进行体内微透析。
溶剂组大鼠能够成功区分新物体和熟悉物体，并且在记忆测试期间PFC中的多巴胺显著增加（p < 0.01）。scPCP导致NOR出现显著缺陷（与对照组相比，p < 0.05），并且未观察到PFC多巴胺增加。
这些数据表明，在记忆测试期间，溶剂组大鼠的多巴胺增加，而scPCP处理的大鼠未观察到这种增加，且scPCP组伴有认知障碍。这一新发现提示了该动物模型中产生认知缺陷的一种机制，并支持其用于研究PFC多巴胺在病理生理学中起核心作用的疾病。
