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Decreased social interaction in the RHA rat model of schizophrenia-relevant features: Modulation by neonatal handling
Behavioural Processes ( IF 1.3 ) Pub Date : 2021-04-20 , DOI: 10.1016/j.beproc.2021.104397
Daniel Sampedro-Viana , Toni Cañete , Francesco Sanna , Bernat Soley , Osvaldo Giorgi , Maria G. Corda , Pilar Torrecilla , Ignasi Oliveras , Carles Tapias-Espinosa , Cristóbal Río-Álamos , Ana Sánchez-González , Adolf Tobeña , Alberto Fernández-Teruel

The Roman-Low (RLA) and High-Avoidance (RHA) rat strains have been bidirectionally selected and bred, respectively, for extremely poor vs. rapid acquisition of the two-way active avoidance task. Over 50 years of selective breeding have led to two strains displaying many differential specific phenotypes. While RLAs display anxious-related behaviours, RHA rats show impulsivity, and schizophrenia-like positive and cognitive symptoms or phenotypes.

Neonatal handling (NH) is an environmental treatment with long-lasting anxiolytic-like and anti-stress effects. NH also reduces symptoms related to schizophrenia, such as pre-pulse inhibition (PPI) impairment and latent inhibition (LI) deficits, and improves spatial working memory and cognitive flexibility.

The present work was aimed at exploring whether RHAs also display negative schizophrenia-like symptoms (or phenotypes), such as lowered preference for social interaction (i.e. asociality), and whether NH would reduce these deficits. To this aim, we evaluated naïve inbred RHA and RLA rats in a social interaction (SI) test after either long- or short-term habituation to the testing set up (studies 1–2). In Study 3 we tested untreated and NH-treated RHA and RLA rats in novel object exploration (NOE) and SI tests. Compared with RHAs, RLA rats displayed increased anxiety-related behaviours in the NOE (i.e. higher behavioural inhibition, lesser exploration of the novel object) and SI (i.e. higher levels of self-grooming) tests which were dramatically reduced by NH treatment, thus supporting the long-lasting anxiolytic-like effect of NH. Remarkably, RHA rats showed decreased social preference in the SI test compared with RLAs, evidencing that RHAs would present a relative asociality, which is thought to model some negative symptomatology (i.e. social withdrawal) of schizophrenia. NH increased absolute levels of social behaviour in both strains, but with a more marked effect in RHA rats, especially in the first 5 min of the SI test. Thus, it is hypothesized that, apart from its effects on anxiety-related behaviours, NH might have long-lasting positive effects on behavioural and neurobiological processes that are impaired in schizophrenia.



中文翻译:

精神分裂症相关特征的RHA大鼠模型中的社交互动减少:新生儿处理的调节

已经分别双向选择和繁殖了罗马低(RLA)和高回避(RHA)大鼠品系,以实现双向主动回避任务的极差与快速采集。超过50年的选择性育种已导致两种菌株表现出许多不同的特异性表型。尽管RLA表现出与焦虑相关的行为,但RHA大鼠表现出冲动性,以及精神分裂症样阳性和认知症状或表型。

新生儿处理(NH)是一种具有长期抗焦虑作用和抗压力作用的环境治疗方法。NH还可以减轻与精神分裂症有关的症状,例如脉冲前抑制(PPI)损伤和潜伏抑制(LI)缺陷,并改善空间工作记忆和认知灵活性。

目前的工作旨在探讨RHA是否还会表现出类似精神分裂症的阴性症状(或表型),例如降低对社交互动的偏好(即社会性),以及NH是否会减少这些缺陷。为此目的,我们在对长期或短期习惯了测试设置的社会交往(SI)测试中评估了未交配的RHA和RLA大鼠(研究1-2)。在研究3中,我们在新对象探索(NOE)和SI测试中测试了未经处理和经NH处理的RHA和RLA大鼠。与RHA相比,RLA大鼠在NOE(即较高的行为抑制力,对新物体的探索较少)和SI(即较高的自我修饰水平)测试中表现出与焦虑相关的行为增加,而NH处理显着降低了焦虑相关行为,从而支持NH的持久抗焦虑作用。值得注意的是 与RLA相比,RHA大鼠在SI测试中显示出较低的社交偏好,表明RHA具有相对的社交性,这被认为可以模拟精神分裂症的某些负面症状(即社交退缩)。NH增加了这两种品系中的社交行为的绝对水平,但在RHA大鼠中具有更显着的作用,尤其是在SI测试的前5分钟。因此,据推测,除了对焦虑相关行为的影响外,NH可能对精神分裂症受损的行为和神经生物学过程具有长期的积极影响。NH增加了这两种品系中的社交行为的绝对水平,但在RHA大鼠中具有更显着的作用,尤其是在SI测试的前5分钟。因此,据推测,除了对焦虑相关行为的影响外,NH可能对精神分裂症受损的行为和神经生物学过程具有长期的积极影响。NH增加了这两种品系中的社交行为的绝对水平,但在RHA大鼠中具有更显着的作用,尤其是在SI测试的前5分钟。因此,据推测,除了对焦虑相关行为的影响外,NH可能对精神分裂症受损的行为和神经生物学过程具有长期的积极影响。

更新日期:2021-05-02
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