Systematic evaluation of skeletal fractures caused by induction of electroconvulsive seizures in rat state a need for attention and refinement of the procedure

Abstract

Electroconvulsive therapy (ECT) is one of the most efficient treatments for major depression. Electroconvulsive seizures (ECS), the animal model of ECT, is widely used to study both mechanisms of action and adverse effects of ECT. As the treatment itself serves as an instant anaesthetic and anaesthetic agents may affect memory functions and behaviour, ECS is traditionally administered without muscle relaxation and anaesthesia. A major problem of unmodified ECS, which has only been addressed peripherally in the literature, is that some animals sustain spinal fractures and subsequent hind leg paralysis (paraplegia). This phenomenon leads to a higher degree of suffering and these animals need to be excluded from the studies. To reach sufficient statistical power, the group sizes are therefore often increased and this may lead to a pre-selected study group in risk of skewing the results. Moreover, the study design of the experiments do not comply with the 3R principles, which advocate for both refinement and reduction of animal experiments. The objective of this study is to systematically evaluate injuries caused by ECS. We summarise the incidence of spinal fractures from 24 studies conducted during 2009–2015 in six different rat strains and report preliminary findings on scapular fractures following auricular ECS. In total, 12.8% of all tested animals suffered from spinal fractures and we find an increase in spinal fracture incidence over time. Furthermore, X-ray analyses revealed that some animals displayed scapular fractures. We discuss consequences of and possible explanations for ECS-induced fractures. Modifications of the method are highly warranted and we furthermore suggest that all animals are thoroughly examined for discrete fractures