背景:过度焦虑是一种精神障碍,它的治疗包括使用苯二氮卓类药物,一类增强GABAA受体上神经递质γ-氨基丁酸(GABA)作用的药物。焦虑症是癫痫患者常见的合并症,据推测,焦虑症和癫痫发作具有共同的神经生物学机制。然而,在戊四唑(PTZ)注射诱导的癫痫动物模型中,有关抗焦虑和抗焦虑作用的结果相互矛盾。这种差异的原因是未知的。我们假设焦虑样行为会根据PTZ点燃过程中发生的癫痫易感性的变化而动态变化。因此,我们试图根据PTZ注射次数双向改变焦虑样行为.
方法:成年雄性大鼠每隔一天注射PTZ20次,根据Racine分期系统对癫痫发作的阶段进行分类。在10次和20次注射后测量焦虑样行为。对照组注射等体积的盐水溶液。焦虑样行为使用开放场进行调查,亮/暗过渡,高架加上迷宫,和社交互动测试。
结果:观察到癫痫发作阶段对PTZ点燃反应的双峰变化。10次注射后,癫痫发作阶段的增加被短暂抑制,这种癫痫敏感性的下降在20次注射后消失了。然而,在20次PTZ注射后,没有大鼠达到完全点燃状态。10次PTZ注射后,与开放领域的对照组相比,焦虑样行为有所减少,亮/暗过渡,和高架迷宫测试。抗焦虑作用与单个大鼠的癫痫发作阶段相关。在20次PTZ注射后,焦虑样行为恢复到控制水平。
结论:PTZ点燃引起癫痫发作阶段的双峰变化。焦虑样行为随着癫痫敏感性的短暂降低而减少,并随着这些状态的消失而恢复到控制水平。这些发现表明了焦虑症和癫痫发作的共同神经生物学机制。此外,以前研究的差异,在PTZ点燃的动物中,焦虑水平增加或减少,可能是由于在点燃过程的不同阶段进行检查。
BACKGROUND: Excessive anxiety is a mental disorder, and its treatment involves the use of benzodiazepines, a class of drugs that enhance the effects of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor. Anxiety disorders are frequent comorbidities in patients with epilepsy, and it has been speculated that anxiety disorders and epileptic seizures share common neurobiological mechanisms. However, conflicting results regarding anxiolytic and anxiogenic effects have been reported in animal models of epilepsy induced by pentylenetetrazole (PTZ) injections, and the causes of this discrepancy are unknown. We hypothesized that anxiety-like behaviors would change dynamically according to the changes in epilepsy susceptibility that occur during the PTZ kindling process. Therefore, we attempted to change anxiety-like behaviors bidirectionally depending on the number of PTZ injections.
METHODS: Adult male rats were injected with PTZ 20 times every other day, and stages of seizure onset were classified according to the Racine staging system. Anxiety-like behaviors were measured after 10 and 20 injections. The control group was injected with an equal volume of saline solution. Anxiety-like behaviors were investigated using the open-field, light/dark transition, elevated plus maze, and social interaction tests.
RESULTS: Bimodal changes in seizure stage were observed in response to PTZ kindling. The increase in the seizure stage was transiently suppressed after 10 injections, and this decrease in epileptic sensitivity disappeared after 20 injections. However, none of the rats reached a fully kindled state after 20 PTZ injections. After 10 PTZ injections, anxiety-like behaviors decreased compared with those of the control group in the open field, light/dark transition, and elevated plus-maze tests. The anxiolytic effects correlated with the seizure stage in individual rats. After 20 PTZ injections, anxiety-like behaviors returned to control levels.
CONCLUSIONS: PTZ kindling induced bimodal changes in the seizure stage. Anxiety-like behaviors decreased with transient decrease in epileptic sensitivity and returned to control levels with the disappearance of these states. These findings suggest a common neurobiological mechanism underlying anxiety disorders and epileptic seizures. In addition, the discrepancy in the previous studies, in which anxiety levels increase or decrease in PTZ-kindled animals, may be due to examination at different phases of the kindling process.