Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil.
Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq/FAPESP/CAPES), Ribeirão Preto, Brazil.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Mar 2;90:169-176. doi: 10.1016/j.pnpbp.2018.11.020. Epub 2018 Nov 28.
The Spontaneously Hypertensive Rat (SHR) strain has been suggested as an animal model of schizophrenia, considering that adult SHRs display behavioral abnormalities that mimic the cognitive, psychotic and negative symptoms of the disease and are characteristic of its animal models. SHRs display: (I) deficits in fear conditioning and latent inhibition (modeling cognitive impairments), (II) deficit in prepulse inhibition of startle reflex (reflecting a deficit in sensorimotor gating, and associated with psychotic symptoms), (III) diminished social behavior (modeling negative symptoms) and (IV) hyperlocomotion (modeling the hyperactivity of the dopaminergic mesolimbic system/ psychotic symptoms). These behavioral abnormalities are reversed specifically by the administration of antipsychotic drugs. Here, we performed a behavioral characterization of young (27-50 days old) SHRs in order to investigate potential early behavioral abnormalities resembling the prodromal phase of schizophrenia. When compared to Wistar rats, young SHRs did not display hyperlocomotion or PPI deficit, but exhibited diminished social interaction and impaired fear conditioning and latent inhibition. These findings are in accordance with the clinical course of schizophrenia: manifestation of social and cognitive impairments and absence of full-blown psychotic symptoms in the prodromal phase. The present data reinforce the SHR strain as a model of schizophrenia, expanding its validity to the prodromal phase of the disorder.
自发性高血压大鼠(SHR)被认为是精神分裂症的动物模型,因为成年 SHR 表现出的行为异常类似于该疾病的认知、精神病和阴性症状,并且是其动物模型的特征。SHR 表现出:(I)恐惧条件反射和潜伏抑制缺陷(模拟认知障碍),(II)惊吓反射前脉冲抑制缺陷(反映感觉运动门控缺陷,与精神病症状相关),(III)社交行为减少(模拟阴性症状)和(IV)过度活跃(模拟多巴胺能中脑边缘系统的过度活跃/精神病症状)。这些行为异常可以通过抗精神病药物的专门给药来逆转。在这里,我们对年轻(27-50 天)SHR 进行了行为特征描述,以研究类似于精神分裂症前驱期的潜在早期行为异常。与 Wistar 大鼠相比,年轻的 SHR 没有表现出过度活跃或 PPI 缺陷,但表现出社交互动减少以及恐惧条件反射和潜伏抑制受损。这些发现与精神分裂症的临床过程相符:在前驱期表现出社交和认知障碍,而没有完全出现精神病症状。本数据进一步证实了 SHR 株作为精神分裂症模型的合理性,扩大了其对该疾病前驱期的有效性。