title: A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.
abstract: 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.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Theilmann
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Socala
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Medical School Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.affiliation: Department of Psychiatry, Social Psychiatry and Psychotherapy, Medical School Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bleich
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine, Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany. Electronic address: claudia.brandt@tiho-hannover.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brandt
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000628:therapy*; D004195:Disease Models, Animal; D004565:Electroconvulsive Therapy / Q000379:methods*; D004569:Electroencephalography; D046353:Immobility Response, Tonic / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012640:Seizures / Q000503:physiopathology; D013550:Swimming / Q000523:psychology; D057170:Translational Research, Biomedical
keywords: Animal model; ECS; ECT; Electroconvulsive therapy; Major depressive disorder; Rat