Journal of Neuroscience Methods 260 (2016) 2–25 Contents lists available at ScienceDirect Journal of Neuroscience Methods jo urnal homepage: www.elsevier.com/locate/jneumeth Basic neuroscience Opportunities for improving animal welfare in rodent models of ଝ epilepsy and seizures a,∗,1 b,1 c,1 d,1 Katie Lidster , John G. Jefferys , Ingmar Blümcke , Vincenzo Crunelli , e,1 f,1 g,1 h,1 Paul Flecknell , Bruno G. Frenguelli , William P. Gray , Rafal Kaminski , i,1 j,1 k,1 l,1 m,1 Asla Pitkänen , Ian Ragan , Mala Shah , Michele Simonato , Andrew Trevelyan , n,1 o,1 p,1 a,1 Holger Volk , Matthew Walker , Neil Yates , Mark J. Prescott a National Centre for Replacement, Refinement and Reduction of Animals in Research (NC3Rs), Gibbs Building, 215 Euston Road, London NW1 2BE, UK b Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK c Institute of Neuropathology, University of Erlangen, Erlangen, Germany d Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, UK e Comparative Biology Centre, Medical School, Newcastle University, Newcastle Upon Tyne, UK f School of Life Sciences, University of Warwick, Coventry, UK g Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff, UK h UCB Pharma, Brussels, Belgium i Department of Neurobiology, Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland j NC3Rs Board, Gibbs Building, 215 Euston Road, London NW1 2BE, UK k UCL School of Pharmacy, University College London, London, UK l Department of Medical Sciences, University of Ferrara, Ferrara, Italy m Institute of Neuroscience, Medical School, Newcastle University, Newcastle upon Tyne, UK n Department of Clinical Science and Services, The Royal Veterinary College, Hatfield, Herts, UK o Institute of Neurology, University College London, London, UK p School of Biomedical Sciences, University of Nottingham, Nottingham, UK h i g h l i g h t s • Report of an expert Working Group to identify opportunities for refining rodent models of epilepsy. • Based upon a survey of epilepsy community, literature review and expert opinion. • Background information and recommendations provided to improve animal welfare. • Practical guidance on refinement opportunities (e.g. induction, recordings, perioperative care). a r t i c l e i n f o a b s t r a c t Article history: Animal models of epilepsy and seizures, mostly involving mice and rats, are used to understand the Received 9 July 2015 pathophysiology of the different forms of epilepsy and their comorbidities, to identify biomarkers, and to Received in revised form 1 September 2015 discover new antiepileptic drugs and treatments for comorbidities. Such models represent an important Accepted 8 September 2015 area for application of the 3Rs (replacement, reduction and refinement of animal use). This report pro- Available online 12 September 2015 vides background information and recommendations aimed at minimising pain, suffering and distress in rodent models of epilepsy and seizures in order to improve animal welfare and optimise the quality Keywords: of studies in this area. The report includes practical guidance on principles of choosing a model, induc- 3Rs tion procedures, in vivo recordings, perioperative care, welfare assessment, humane endpoints, social Animal model Epilepsy housing, environmental enrichment, reporting of studies and data sharing. In addition, some model- Mouse specific welfare considerations are discussed, and data gaps and areas for further research are identified. Rat The guidance is based upon a systematic review of the scientific literature, survey of the international Refinement epilepsy research community, consultation with veterinarians and animal care and welfare officers, Seizure ଝ Report of a Working Group of the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). ∗ Corresponding author. Tel.: +44 2076112279. E-mail address: [email protected] (K. Lidster). 1 All authors are members of the NC3Rs working group on mammalian models of epilepsy (www.nc3rs.org.uk/epilepsy). http://dx.doi.org/10.1016/j.jneumeth.2015.09.007 0165-0270/© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4. 0/). K. Lidster et al. / Journal of Neuroscience Methods 260 (2016) 2–25 3 and the expert opinion and practical experience of the members of a Working Group convened by the United Kingdom’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Contents 1. Introduction . 3 1.1. Background . 3 1.2. Working group aims and scope . 4 1.3. Report audience and contents . 4 1.4. Methodology . 4 1.5. Limitations of methodology . 5 2. Animal models used in epilepsy research . 5 2.1. Area of epilepsy research . 5 2.2. Species and models used . 5 2.3. Choice of animal model. .5 3. General principles for refinement. .6 3.1. Considerations in the choice of animal model . 6 3.2. Induction procedures . 8 3.3. In vivo recordings . 8 3.4. Perioperative care . 9 3.5. Welfare assessment . 11 3.6. Humane endpoints . 12 3.7. Social housing . 13 3.8. Environmental enrichment . 14 3.9. Reporting and data sharing . 15 4. Model-specific welfare considerations . 15 4.1. Models dependent on initial SE . 18 4.2. Models not involving SE. ..