Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
J Psychiatr Res. 2014 Jun;53:94-8. doi: 10.1016/j.jpsychires.2014.02.007. Epub 2014 Feb 19.
Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT.
电抽搐疗法是治疗重度抑郁症（MDD）最有效的疗法。在以前对抗抑郁药物有抗药性的患者中，缓解率超过 50%，但作用机制尚不完全清楚。电抽搐刺激（ECS）在啮齿动物中模拟抗抑郁电抽搐疗法（ECT），被广泛用于研究 ECT 的潜在机制。为了使动物模型中的发现具有转化价值，至关重要的是建立具有尽可能高的结构、表面和预测有效性的模型。啮齿动物中常用的 ECT 模型不符合高结构有效性的要求。对于 ECT，使用皮质表面电极来诱发治疗性癫痫发作，而 ECS 在啮齿动物中仅通过耳或角膜电极进行。然而，刺激部位对诱发的癫痫活动的类型和传播及其抗抑郁作用有重大影响。我们提出了一种方法，即用放置在大鼠运动皮质上方的螺丝电极进行 ECS，以紧密模拟临床情况，从而提高模型的结构有效性。皮质 ECS 在大鼠中可靠地诱导了类似于人类 ECT 的癫痫发作。皮质 ECS 比耳 ECS 更有效地减少强迫游泳试验中的不动性。重要的是，耳刺激对大鼠的整体健康状况产生了负面影响，在刺激过程中出现了恐惧迹象。这些结果表明，大鼠的耳 ECS 不是一种合适的 ECT 模型。皮质 ECS 在大鼠中有望成为模拟 ECT 的有效方法。
