یک روش جدید برای الکتروشوک درمانی مدل سازی در موش با افزایش اعتبار ساخت و افزایش ارزش انتقالی

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.

Electroconvulsive therapy (ECT) is the most effective therapy for pharmacoresistant major depressive disorder (MDD) (The UK ECT Review group, 2003 and Heijnen et al., 2010). The use of ECT has constantly increased over the last decade but still the mechanisms of action are not fully understood. Clarification of the underlying mechanism leading to the therapeutic effect of ECT could significantly contribute to the understanding of the pathogenesis of MDD and the development of improved treatment strategies. Although new possibilities open up for non-invasive investigations in humans with improving imaging techniques many questions can only be addressed in animal models using invasive methods. A prerequisite to obtain data from animal research with high translational value is the validity of the model. Already in 1969, McKinney and Bunney proposed validating criteria to evaluate the translational value of models for mental diseases. Willner (1984) applied these criteria on animal models of depression which lead to an ongoing effort to improve such models for the highest validity possible. Electroconvulsive stimulations (ECS) in rats or mice are used to mimic ECT. Although ECS is a model for a treatment method and not a model for depression it is not less important to fulfil the validating criteria to obtain a high translational value. So far, experimental research is based almost exclusively on models in which rodents are treated with electroconvulsive stimulations (ECS) via auricular or, less often, corneal electrodes. In the clinical ECT setting the electrical stimulation is performed via cortical surface electrodes. It is well known that the electrode placement has a significant impact on the consequences of the induced seizure activity with respect to various parameters such as seizure type, pharmacological responsiveness and biochemical changes (e.g. Browning and Nelson, 1985, Isaac et al., 1985, Ferraro et al., 1990 and Löscher et al., 1991). Therefore, it is more than likely that the different placement of stimulation electrodes in humans and rodents has a significant impact on the translational value of the results because the construct validity of ECS in rodents is not given. The aim of the present study is to propose an ECS method in rats using cortical screw electrodes placed above the frontal cortex which simulates the bifrontal ECT in humans. The cortical ECS was compared with the traditional auricular ECS with respect to seizure parameters and acute and chronic effects on well being and behaviour of the rats.