Abstract：
At the Institute of Cytology and Genetics (Novosibirsk, Russia) for over 85 generations, gray rats have been selected for high aggression toward humans (aggressive rats) or its complete absence (tame rats). Aggressive rats are an interesting model for studying fear-induced aggression. Benzopentathiepin TC-2153 exerts an antiaggressive effect on aggressive rats and affects the serotonergic system: an important regulator of aggression. The aim of this study was to investigate effects of TC-2153 on key serotonergic-system enzymes - tryptophan hydroxylase 2 (TPH2) and monoamine oxidase A (MAOA) - in the brain of aggressive and tame rats. Either TC-2153 (10 or 20 mg/kg) or vehicle was administered once intraperitoneally to aggressive and tame male rats. TPH2 and MAOA enzymatic activities and mRNA and protein levels were assessed. The selection for high aggression resulted in upregulation of Tph2 mRNA in the midbrain, of the TPH2 protein in the hippocampus, and of proteins TPH2 and MAOA in the hypothalamus, as compared to tame rats. MAO enzymatic activity was higher in the midbrain and hippocampus of aggressive rats while TPH2 activity did not differ between the strains. The single TC-2153 administration decreased TPH2 and MAO activity in the hypothalamus and midbrain, respectively. The drug affected MAOA protein levels in the hypothalamus: upregulated them in aggressive rats and downregulated them in tame ones. Thus, this study shows profound differences in the expression and activity of key serotonergic system enzymes in the brain of rats selectively bred for either highly aggressive behavior toward humans or its absence, and the effects of benzopentathiepin TC-2153 on these enzymes may point to mechanisms of its antiaggressive action.
摘要：
在细胞学和遗传学研究所（新西伯利亚，俄罗斯)超过85代，灰色大鼠已选择对人类的高攻击性（攻击性大鼠）或其完全不存在（驯服大鼠）。攻击性大鼠是研究恐惧引起的攻击性的有趣模型。苯并谷胱甘肽TC-2153对侵袭性大鼠具有抗侵袭作用，并影响血清素能系统：侵略的重要调节剂。这项研究的目的是研究TC-2153对攻击性和驯服大鼠大脑中关键的血清素能系统酶-色氨酸羟化酶2（TPH2）和单胺氧化酶A（MAOA）的影响。向侵袭性和驯服的雄性大鼠腹膜内施用一次TC-2153(10或20mg/kg)或媒介物。评估了TPH2和MAOA的酶活性以及mRNA和蛋白质水平。选择高攻击性导致中脑Tph2mRNA上调，海马中的TPH2蛋白，以及下丘脑中的蛋白质TPH2和MAOA，与驯服的老鼠相比。侵袭性大鼠的中脑和海马中MAO酶活性较高，而TPH2活性在菌株之间没有差异。单一的TC-2153给药降低了下丘脑和中脑的TPH2和MAO活性,分别。该药物影响下丘脑中的MAOA蛋白水平：在攻击性大鼠中上调它们，在驯服大鼠中下调它们。因此，这项研究表明，在大脑中的关键血清素能系统酶的表达和活性存在着深刻的差异，这些酶是针对对人类的高度攻击行为或其缺失而选择性饲养的，苯并谷胱甘肽TC-2153对这些酶的影响可能指向其抗侵袭作用的机制。
