PDF(Pubmed)
Abstract：
The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines/strains were established in Rome through bidirectional selection of Wistar rats for rapid (RHA) or extremely poor (RLA) acquisition of a two-way active avoidance task. Relative to RHAs, RLA rats exhibit enhanced threat sensitivity, anxiety, fear and vulnerability to stress, a passive coping style and increased sensitivity to frustration. Thus, RLA rats\' phenotypic profile falls well within the \"internalizing\" behavior spectrum. Compared with RLAs and other rat strains/stocks, RHAs present increased impulsivity and reward sensitivity, deficits in social behavior and attentional/cognitive processes, novelty-induced hyper-locomotion and vulnerability to psychostimulant sensitization and drug addiction. Thus, RHA rats\' phenotypes are consistent with a \"disinhibiting externalizing\" profile. Many neurobiological/molecular traits differentiate both rat lines/strains. For example, relative to RLA rats, RHAs exhibit decreased function of the prefrontal cortex (PFC), hippocampus and amygdala, increased functional tone of the mesolimbic dopamine system, a deficit of central metabotropic glutamate-2 (mGlu2) receptors, increased density of serotonin 5-HT2A receptors in the PFC, impairment of GABAergic transmission in the PFC, alterations of several synaptic markers and increased density of pyramidal immature dendrític spines in the PFC. These characteristics suggest an immature brain of RHA rats and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. We review evidence supporting RLA rats as a valid model of anxiety/fear, stress and frustration vulnerability, whereas RHA rats represent a promising translational model of neurodevelopmental alterations related to impulsivity, schizophrenia-relevant features and comorbidity with drug addiction vulnerability.
摘要：
通过双向选择Wistar大鼠以快速（RHA）或极差（RLA）获得双向主动回避任务，在罗马建立了罗马高回避（RHA）和低回避（RLA）大鼠品系/品系。相对于RHAs,RLA大鼠表现出增强的威胁敏感性，焦虑,恐惧和脆弱的压力，被动的应对方式和对挫折的敏感性增加。因此，RLA大鼠的表型谱完全属于“内在化”行为谱。与RLA和其他大鼠品系/股票相比，RHAs表现出增加的冲动性和奖励敏感性，社会行为和注意力/认知过程的缺陷，新颖性引起的运动过度和对精神兴奋剂致敏和药物成瘾的脆弱性。因此，RHA大鼠的表型与“去抑制外部化”概况一致。许多神经生物学/分子特征区分两种大鼠系/品系。例如,相对于RLA大鼠，RHAs表现出前额叶皮质（PFC）的功能降低，海马体和杏仁核,增加了中脑边缘多巴胺系统的功能色调，中枢代谢型谷氨酸-2（mGlu2）受体缺乏，PFC中5-羟色胺5-HT2A受体的密度增加，PFC中GABA能传递的损害，PFC中几种突触标记物的改变和锥体未成熟树突棘的密度增加。这些特征表明RHA大鼠的大脑不成熟，并让人想起精神分裂症的特征，例如过度和兴奋/抑制皮层平衡的破坏。我们回顾了支持RLA大鼠作为焦虑/恐惧有效模型的证据，压力和挫折的脆弱性，而RHA大鼠代表了与冲动相关的神经发育改变的有希望的转化模型，精神分裂症相关特征和合并症与药物成瘾易感性。
