Dombrowski Patrícia A, Fernandes Lineane H, Andreatini Roberto
Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico C.P. 19031, 81540-990 Curitiba, PR, Brazil.
Eur J Pharmacol. 2006 May 10;537(1-3):72-6. doi: 10.1016/j.ejphar.2006.03.037. Epub 2006 Mar 24.
The effect of acute sodium valproate administration, an anxiolytic and putative panicolytic drug, was evaluated in rats tested in the elevated T-maze, an animal model that measures two defensive reactions: avoidance (inhibitory avoidance), related to generalized anxiety, and escape (escape from open arms), related to panic. Additionally, the involvement of gamma-aminobutyric acid (GABA) neurotransmission in sodium valproate effects was studied by picrotoxin co-administration. Sodium valproate (300 mg/kg, intraperitoneally, 30 min before the test) impaired both avoidance latency (time to leave the closed arm) and one-way escape (latency to enter the closed arm) indicating anxiolytic and panicolytic effects, respectively. Pre-treatment with picrotoxin (0.5 mg/kg, intraperitoneally, 5 min before sodium valproate administration) blocked the effects of sodium valproate on inhibitory avoidance and one-way escape. No locomotor effect was seen in the open-field. These data suggest that sodium valproate exerts anxiolytic-like and panicolytic-like effects in the elevated T-maze and that these effects were mediated by picrotoxin-sensitive GABA type A receptors.
在高架T型迷宫中对大鼠进行测试，评估了急性给予丙戊酸钠（一种抗焦虑和假定的抗惊恐药物）的效果。高架T型迷宫是一种动物模型，可测量两种防御反应：与广泛性焦虑相关的回避（抑制性回避），以及与惊恐相关的逃脱（从开放臂逃脱）。此外，通过联合给予印防己毒素，研究了γ-氨基丁酸（GABA）神经传递在丙戊酸钠作用中的参与情况。丙戊酸钠（300mg/kg，腹腔注射，在测试前30分钟）分别损害了回避潜伏期（离开封闭臂的时间）和单向逃脱（进入封闭臂的潜伏期），表明其具有抗焦虑和抗惊恐作用。在给予丙戊酸钠前5分钟腹腔注射印防己毒素（0.5mg/kg）预处理，可阻断丙戊酸钠对抑制性回避和单向逃脱的作用。在旷场试验中未观察到运动效应。这些数据表明，丙戊酸钠在高架T型迷宫中发挥抗焦虑样和抗惊恐样作用，且这些作用由对印防己毒素敏感的A型GABA受体介导。
