Porsolt SAS, ZA de Glatigné, 53940, Le Genest-Saint-Isle, France.
Psychopharmacology (Berl). 2021 Feb;238(2):517-528. doi: 10.1007/s00213-020-05700-y. Epub 2020 Nov 9.
There is a need to develop animal models of schizophrenia-like behaviors that have both construct and predictive validity. Recently, a neonatal phencyclidine (PCP) and post-weaning social isolation dual-hit model was developed; however, its face and predictive validities need to be further investigated.
The aims of this study were to extend the characterization of the behavioral changes occurring in the neonatal PCP and post-weaning social isolation dual-hit rat model and to evaluate the effects of chronic treatment with clozapine on signs related to schizophrenia.
Male Wistar rat pups were treated with PCP (10 mg/kg s.c.) on postnatal days (PND) 7, 9, and 11. Starting from weaning, neonatal PCP-treated rat pups were socially isolated, while control saline-treated rats were group housed. At adulthood, rats were assessed using behavioral tasks evaluating locomotor activity, social recognition, prepulse inhibition, and reversal learning. Clozapine (3 mg/kg i.p.) was administered daily starting from a week before behavioral tests and until the end of the study.
Neonatal PCP-treated and post-weaning social isolated (PCP-SI) rats displayed persistent and robust locomotor hyperactivity as well as social recognition impairment. The latter could not be explained by variations in the motivation to interact with a juvenile rat. Weak-to-moderate deficits in prepulse inhibition and reversal learning were also observed. Chronic treatment with clozapine attenuated the observed locomotor hyperactivity and social recognition deficits.
The PCP-SI model presents enduring and robust deficits (hyperactivity and social recognition impairment) associated with positive symptoms and cognitive/social deficits of schizophrenia, respectively. These deficits are normalized by chronic treatment with clozapine, thereby confirming the predictive validity of this animal model.
开发具有构建和预测效度的类似精神分裂症行为的动物模型是有必要的。最近，开发了一种新生期苯环己哌啶（PCP）和断奶后社交隔离双重打击模型；然而，其表面效度和预测效度仍需进一步研究。
本研究旨在扩展新生期 PCP 和断奶后社交隔离双重打击大鼠模型中发生的行为变化的特征，并评估氯氮平的慢性治疗对与精神分裂症相关的症状的影响。
雄性 Wistar 幼鼠在出生后第 7、9 和 11 天接受 PCP（10mg/kg sc）治疗。从断奶开始，新生期 PCP 处理的幼鼠被社交隔离，而对照生理盐水处理的幼鼠则被分组饲养。成年后，使用评估运动活动、社会识别、预脉冲抑制和反转学习的行为任务对大鼠进行评估。氯氮平（3mg/kg ip）从行为测试前一周开始每天给药，直到研究结束。
新生期 PCP 处理和断奶后社交隔离（PCP-SI）大鼠表现出持久和强烈的运动过度活跃以及社会识别障碍。后者不能用与幼鼠互动的动机变化来解释。预脉冲抑制和反转学习也存在弱至中度缺陷。氯氮平的慢性治疗减轻了观察到的运动过度活跃和社会识别缺陷。
PCP-SI 模型呈现出持久和强烈的缺陷（过度活跃和社会识别障碍），分别与精神分裂症的阳性症状和认知/社会缺陷相关。这些缺陷通过氯氮平的慢性治疗得到纠正，从而证实了该动物模型的预测效度。
