Azechi Hirotsugu, Hakamada Kōsuke, Yamamoto Takanobu
Department of Psychology, Tezukayama University, Nara 631-8585, Japan.
Department of Neurophysiology and Cognitive Neuroscience, Graduate School of Psychological Sciences, Tezukayama University, Nara 631-8585, Japan.
IBRO Rep. 2019 Nov 6;7:98-106. doi: 10.1016/j.ibror.2019.11.001. eCollection 2019 Dec.
The Fawn-Hooded (FH) rat carries a gene mutation that results in a dysfunctional serotoninergic system. However, previous studies have reported differing features between the FH/Wjd and FH/Har strains. We aimed to compare the behavioural and neurobiological features of FH/HamSlc rats with those of Fischer 344 rats. We performed the open field, elevated minus-maze, Y-maze spontaneous alternation, and forced swim tests to investigate behavioural alterations. We also assessed neurobiological characteristics by quantifying monoamines and their related compounds in the prefrontal cortex, hippocampus, and striatum using high-performance liquid chromatography with an electrochemical detection system. FH/HamSlc rats showed hyperactivity and a high impulsivity tendency in the open field and the elevated minus maze test, but no cognitive dysfunction. In addition, the hyperactivity was suppressed immediately after the forced swim test. FH/HamSlc rats showed low dopamine levels, but high dopamine turnover in the striatum. Serotonin and noradrenaline levels were low in the prefrontal cortex and the hippocampus of FH/HamSlc rats, but high serotonin turnover was observed in the prefrontal cortex, hippocampus, and striatum. FH/HamSlc rats show (1) mania-like behavioural characteristics that are different from those of other strains of FH rats; (2) stimulus dependent suppression of hyperactivity similar to the clinical findings that exercise alleviates the symptoms of bipolar disorder; and (3) monoaminergic dysregulation such as monoamine imbalance and hyperturnover that may be associated with mania-related behavioural characteristics. Thus, the FH/HamSlc rat is a new animal model for mania including bipolar disorder.
小鹿斑比帽状(FH)大鼠携带一种基因突变,导致血清素能系统功能失调。然而,先前的研究报告了FH/Wjd和FH/Har品系之间存在不同特征。我们旨在比较FH/HamSlc大鼠与Fischer 344大鼠的行为和神经生物学特征。我们进行了旷场试验、高架十字迷宫试验、Y迷宫自发交替试验和强迫游泳试验,以研究行为改变。我们还通过使用带有电化学检测系统的高效液相色谱法,定量前额叶皮质、海马体和纹状体中的单胺及其相关化合物,来评估神经生物学特征。FH/HamSlc大鼠在旷场试验和高架十字迷宫试验中表现出多动和高冲动倾向,但没有认知功能障碍。此外,强迫游泳试验后多动立即受到抑制。FH/HamSlc大鼠纹状体中的多巴胺水平较低,但多巴胺周转率较高。FH/HamSlc大鼠前额叶皮质和海马体中的血清素和去甲肾上腺素水平较低,但在前额叶皮质、海马体和纹状体中观察到高血清素周转率。FH/HamSlc大鼠表现出:(1)与其他品系FH大鼠不同的躁狂样行为特征;(2)类似于运动缓解双相情感障碍症状的临床发现的刺激依赖性多动抑制;(3)可能与躁狂相关行为特征有关的单胺能失调,如单胺失衡和高周转率。因此,FH/HamSlc大鼠是一种包括双相情感障碍在内的躁狂症新动物模型。