Department of Pharmacology, Universidade Federal de São Paulo. Rua Pedro de Toledo, 669, 5° andar, Ed. de Pesquisas II, CEP 04039-032, São Paulo, SP, Brazil.
Behav Brain Res. 2011 Nov 20;225(1):15-22. doi: 10.1016/j.bbr.2011.06.026. Epub 2011 Jun 30.
We have recently reported that spontaneously hypertensive rats (SHRs) exhibit a deficit in contextual fear conditioning that is specifically reversed by antipsychotic and potentiated by psychostimulants and other manipulations thought to produce schizophrenia-like states in rodents. Based on these findings, we suggested that this deficit in fear conditioning could be used as an experimental model of emotional processing impairments observed in schizophrenia. This strain has also been suggested as a model by which to study attention deficit/hyperactivity disorder (ADHD). Considering that schizophrenia and ADHD are both characterized by poor social function, this study aimed to investigate possible behavioral deficits of SHRs in a social context. Furthermore, we sought to examine the effects of typical and atypical antipsychotics (used for the treatment of schizophrenia) and a psychostimulant (used to treat ADHD) on these behaviors. Pairs of unfamiliar rats of the same or different (i.e., Wistar) strains were treated with one of the aforementioned drugs and placed in an open-field for 10min. During this time, social behaviors, locomotion and rearing frequencies were scored. Atypical antipsychotics increased social interaction in Wistar rats (WRs) and improved the deficit in social interaction exhibited by SHRs. In addition, the SHR group displayed hyperlocomotion that was attenuated by all antipsychotics (quetiapine and clozapine also decreased locomotion in WRs) and potentiated by amphetamine (which also increased locomotion in WRs). Our results reveal that the behavioral profile of the SHR group demonstrates that this strain can be a useful animal model to study several aspects of schizophrenia.
我们最近报道称，自发性高血压大鼠（SHR）在情境性恐惧条件反射中存在缺陷，这种缺陷可以被抗精神病药物特异性逆转，而被精神兴奋剂和其他被认为能在啮齿动物中产生类似精神分裂症状态的操作增强。基于这些发现，我们认为这种恐惧条件反射的缺陷可以作为精神分裂症中观察到的情绪处理障碍的实验模型。这种品系也被建议作为研究注意力缺陷多动障碍（ADHD）的模型。鉴于精神分裂症和 ADHD 均以社会功能不良为特征，本研究旨在调查 SHR 在社会环境中的可能行为缺陷。此外，我们还试图研究典型和非典型抗精神病药（用于治疗精神分裂症）和精神兴奋剂（用于治疗 ADHD）对这些行为的影响。同一或不同（即 Wistar）品系的陌生大鼠成对接受上述药物之一的治疗，并置于开阔场中 10min。在此期间，对社会行为、运动和站立频率进行评分。非典型抗精神病药增加了 Wistar 大鼠（WRs）的社交互动，并改善了 SHRs 表现出的社交互动缺陷。此外，SHR 组表现出过度运动，所有抗精神病药（喹硫平和氯氮平也降低了 WRs 的运动）都减弱了这种过度运动，而安非他命增强了这种过度运动（安非他命也增加了 WRs 的运动）。我们的结果表明，SHR 组的行为特征表明，该品系可以作为研究精神分裂症几个方面的有用动物模型。
