Paltian Jaini J, Dos Reis Angélica S, de Oliveira Renata L, da Fonseca Caren A R, Domingues William B, Dellagostin Eduardo N, Campos Vinícius F, Kruger Roberta, Alves Diego, Luchese Cristiane, Wilhelm Ethel A
Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Programa de Pós-graduação em Biotecnologia, Laboratório de Genômica Estrutural, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Behav Brain Res. 2020 Sep 1;393:112797. doi: 10.1016/j.bbr.2020.112797. Epub 2020 Jul 7.
Recently, we demonstrated the promising anxiolytic action of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) in mice. For this reason, the objective of this study was to expand our previous findings by investigating the contribution of serotoninergic and GABAergic systems to the anxiolytic action of this compound. Pretreatment with different serotoninergic antagonists (pindolol, WAY100635 and ketanserin) blocked the anxiolytic effect caused by 4-PSQ (50 mg/kg, per oral) in the elevated plus maze (EPM) test. The contribution of the GABAergic system was investigated by pretreatment with pentylenetetrazole (a GABA receptor antagonist) (PTZ). 4-PSQ diminished the PTZ-induced anxiety, and did not modify the locomotor, exploratory and motor activities of mice. Later, this group of animals was euthanized and the blood was removed to determine the levels of corticosterone, and cerebral cortex and hippocampus to determine the mRNA expression levels of cAMP response element binding protein (CREB), brain derived neurotrophic factor (BDNF) and nuclear factor kappa B (NF-κB), as well as the Na, K ATPase activity and reactive species (RS) levels. 4-PSQ was able to significantly reverse the increase in RS and corticosterone levels, as well as the decrease of CREB and BDNF expression in the cerebral structures and increase of NF-κB expression in the hippocampus. Finally, 4-PSQ restored the Na, K ATPase activity in the cerebral structures evaluated. Here, we showed that the modulation of serotonergic and GABAergic systems, factors related to neurogenesis, oxidative status and Na, K ATPase activity contributes to the anxiolytic effect of 4-PSQ and reinforces the therapeutical potential of this compound for the treatment of anxiety.
最近，我们证明了7-氯-4-（苯硒基）喹啉（4-PSQ）在小鼠中具有有前景的抗焦虑作用。因此，本研究的目的是通过研究5-羟色胺能和γ-氨基丁酸能系统对该化合物抗焦虑作用的贡献来扩展我们之前的发现。在高架十字迷宫（EPM）试验中，用不同的5-羟色胺能拮抗剂（吲哚洛尔、WAY100635和酮色林）预处理可阻断4-PSQ（50mg/kg，口服）引起的抗焦虑作用。通过用戊四氮（一种γ-氨基丁酸受体拮抗剂）（PTZ）预处理来研究γ-氨基丁酸能系统的作用。4-PSQ减轻了PTZ诱导的焦虑，并且未改变小鼠的运动、探索和活动能力。随后，对这组动物实施安乐死并取血以测定皮质酮水平，取大脑皮层和海马以测定环磷酸腺苷反应元件结合蛋白（CREB）、脑源性神经营养因子（BDNF）和核因子κB（NF-κB）的mRNA表达水平，以及钠钾ATP酶活性和活性物质（RS）水平。4-PSQ能够显著逆转RS和皮质酮水平的升高，以及大脑结构中CREB和BDNF表达的降低和海马中NF-κB表达的增加。最后，4-PSQ恢复了所评估的大脑结构中的钠钾ATP酶活性。在此，我们表明5-羟色胺能和γ-氨基丁酸能系统的调节、与神经发生、氧化状态和钠钾ATP酶活性相关的因素有助于4-PSQ的抗焦虑作用，并增强了该化合物治疗焦虑症的治疗潜力。
