Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
J Psychopharmacol. 2019 Oct;33(10):1274-1287. doi: 10.1177/0269881119844196. Epub 2019 May 7.
Cognitive deficits and structural brain changes co-occur in patients with schizophrenia. Improving our understanding of the relationship between these is important to develop improved therapeutic strategies. Back-translation of these findings into rodent models for schizophrenia offers a potential means to achieve this goal.
The purpose of this study was to determine the extent of structural brain changes and how these relate to cognitive behaviour in a sub-chronic phencyclidine rat model.
Performance in the novel object recognition task was examined in female Lister Hooded rats at one and six weeks after sub-chronic phencyclidine (2 mg/kg intra-peritoneal, 15) and saline controls (1 ml/kg intra-peritoneal, 15). Locomotor activity following acute phencyclidine challenge was also measured. Brain volume changes were assessed in the same animals using ex vivo structural magnetic resonance imaging and computational neuroanatomical analysis at six weeks.
Female sub-chronic phencyclidine-treated Lister Hooded rats spent significantly less time exploring novel objects (0.05) at both time-points and had significantly greater locomotor activity response to an acute phencyclidine challenge (0.01) at 3-4 weeks of washout. At six weeks, sub-chronic phencyclidine-treated Lister Hooded rats displayed significant global brain volume reductions (0.05; 0.05), without apparent regional specificity. Relative volumes of the perirhinal cortex however were positively correlated with novel object exploration time only in sub-chronic phencyclidine rats at this time-point.
A sustained sub-chronic phencyclidine-induced cognitive deficit in novel object recognition is accompanied by global brain volume reductions in female Lister Hooded rats. The relative volumes of the perirhinal cortex however are positively correlated with novel object exploration, indicating some functional relevance.
认知缺陷和结构脑变化在精神分裂症患者中同时发生。深入了解两者之间的关系对于开发改善的治疗策略很重要。将这些发现反向翻译为精神分裂症的啮齿动物模型提供了实现这一目标的潜在手段。
本研究旨在确定亚慢性苯环己哌啶大鼠模型中的结构脑变化程度以及这些变化与认知行为的关系。
在亚慢性苯环己哌啶（2mg/kg 腹腔内，15 次）和盐水对照（1ml/kg 腹腔内，15 次）后 1 周和 6 周，通过新物体识别任务检查雌性 Lister Hooded 大鼠的行为表现。还测量了急性苯环己哌啶挑战后的运动活动。在相同的动物中，使用离体结构磁共振成像和计算神经解剖学分析，在 6 周时评估脑体积变化。
在两个时间点，雌性亚慢性苯环己哌啶处理的 Lister Hooded 大鼠探索新物体的时间明显减少（0.05），在 3-4 周洗脱期时对急性苯环己哌啶挑战的运动活动反应明显增加（0.01）。在 6 周时，亚慢性苯环己哌啶处理的 Lister Hooded 大鼠显示出明显的全脑体积减少（0.05；0.05），但没有明显的区域特异性。然而，在这个时间点，只有在亚慢性苯环己哌啶大鼠中，杏仁旁皮质的相对体积与新物体探索时间呈正相关。
在雌性 Lister Hooded 大鼠中，持续的亚慢性苯环己哌啶诱导的新物体识别认知缺陷伴随着全脑体积减少。然而，杏仁旁皮质的相对体积与新物体探索呈正相关，表明具有一定的功能相关性。
