焦虑是一种严重的精神障碍,最近的统计数据确定,在COVID-19大流行期间,全球35.12%的人口患有焦虑症。与抗焦虑作用相关的机制与烟碱乙酰胆碱受体(nAChR)激动剂有关,主要作用于α4β2nAChR亚型。nAChRs存在于不同的动物模型中,包括鼠类和硬骨鱼。斑马鱼由于其高的人类基因相似性(70%)而成为理想的动物模型,赋予它在不同研究领域的高度通用性,其中包括与焦虑相关的行为研究。新型坦克潜水测试(NTT)是用于研究与抗焦虑作用相关的新药的众多范例之一。在这项工作中,成年斑马鱼被用来确定3-和5-卤代胺衍生物的行为效应,使用不同剂量的NTT。我们的结果表明,与对照相比,在第3位被氯或溴取代减少了鱼在底部花费的时间。然而,较高剂量的3-氯衍生物增加了底部停留时间。相比之下,在该模型中,在5位的替代增加了在所有浓度下的底部滞留,没有抗焦虑作用。用5-氯胞嘧啶衍生物观察到意想不到的结果,浓度为10mg/L时,底部停留时间显着减少,并显示出高冻结时间。总之,3-氯和3-溴衍生物显示抗焦虑作用,3-氯胞嘧啶衍生物比3-溴衍生物更有效,罐底的最低时间为1mg/L。另一方面,氯,和5位的溴产生相反的效果。
Anxiety is a serious mental disorder, and recent statistics have determined that 35.12% of the global population had an anxiety disorder during the COVID-19 pandemic. A mechanism associated with anxiolytic effects is related to nicotinic acetylcholine receptor (nAChR) agonists, principally acting on the α4β2 nAChR subtype. nAChRs are present in different animal models, including murine and teleosteos ones. Zebrafish has become an ideal animal model due to its high human genetic similarities (70%), giving it high versatility in different areas of study, among them in behavioral studies related to anxiety. The novel tank diving test (NTT) is one of the many paradigms used for studies on new drugs related to their anxiolytic effect. In this work, an adult zebrafish was used to determine the behavioral effects of 3- and 5-halocytisine derivatives, using the NTT at different doses. Our results show that substitution at position 3 by chlorine or bromine decreases the time spent by the fish at the bottom compared to the control. However, the 3-chloro derivative at higher doses increases the bottom dwelling time. In contrast, substitution at the 5 position increases bottom dwelling at all concentrations showing no anxiolytic effects in this model. Unexpected results were observed with the 5-chlorocytisine derivative, which at a concentration of 10 mg/L produced a significant decrease in bottom dwelling and showed high times of freezing. In conclusion, the 3-chloro and 3-bromo derivatives show an anxiolytic effect, the 3-chlorocytisine derivative being more potent than the 3-bromo derivative, with the lowest time at the bottom of the tank at 1mg/L. On the other hand, chlorine, and bromine at position 5 produce an opposite effect.