{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T13:31:23Z","timestamp":1740144683527,"version":"3.37.3"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["313-99-310"],"award-info":[{"award-number":["313-99-310"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Philos Ethics Humanit Med"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Current policies regulating the use of animals for scientific purposes are based on balancing between potential gain of knowledge and suffering of animals used in experimentation. The balancing process is complicated, on the one hand by plurality of views on our duties towards animals, and on the other hand by more recent discussions on uncertainty in the probability of reaching the final aim of the research and problems of translational failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study combines ethical analysis based on a literature review with neuropsychiatry-related preclinical research as a case study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Based on the analysis and the case study we show that neuropsychiatry-related preclinical research is an especially interesting case from an ethical perspective. The 3R principles (Replacement, Reduction and Refinement) are used to minimize the negative consequences for the animals used in research. However, neuropsychiatric research is characterized by specific challenges in assessing the probability of success of reaching the final aim, due to our limited mechanistic knowledge of human neuropsychiatric illness. Consequently, the translational value of the currently used animal models may be difficult to prove, which undermines the validity of these models and complicated the ethical assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We conclude that a combined approach that deals with both science and the ethical dimensions is necessary to address the problems of validity and translation in neuropsychiatry-related preclinical research. We suggest this approach to comprise first, improved experimental methods, e.g. by using systematic reviews, second, a more patients-based approach that leads to models that reflect interindividual variation better, and third, more interdisciplinary cooperation.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13010-019-0085-4","type":"journal-article","created":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:05:34Z","timestamp":1579737934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Joining forces: the need to combine science and ethics to address problems of validity and translation in neuropsychiatry research using animal models"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0752-016X","authenticated-orcid":false,"given":"Franck L. B.","family":"Meijboom","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elzbieta","family":"Kostrzewa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathalijn H. C.","family":"Leenaars","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"85_CR1","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.shpsc.2010.07.002","volume":"41","author":"C Shelley","year":"2010","unstructured":"Shelley C. Why test animals to treat humans? On the validity of animal models. Stud Hist Phil Biol Biomed Sci. 2010;41:292\u20139.","journal-title":"Stud Hist Phil Biol Biomed Sci"},{"key":"85_CR2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/7854_2014_319","volume":"19","author":"AC Vieira de Castro","year":"2015","unstructured":"Vieira de Castro AC, Olsson IAS. Does the Goal Justify the Methods? Harm and Benefit in Neuroscience Research Using Animals. Curr Top Behav Neurosci. 2015;19:47\u201378. https:\/\/doi.org\/10.1007\/7854_2014_319.","journal-title":"Curr Top Behav Neurosci"},{"key":"85_CR3","volume-title":"The ethics of research involving animals","author":"Nuffield Council","year":"2005","unstructured":"Nuffield Council. Nuffield Council on Bioethics. In: The ethics of research involving animals; 2005."},{"key":"85_CR4","doi-asserted-by":"publisher","unstructured":"Meijboom F. Applying Ethical Thinking and Social Relevance. In H. R\u00f6cklinsberg, M. Gjerris, & I. Olsson (Authors), Animal Ethics in Animal Research. Cambridge: Cambridge University Press; 2017. pp. 41\u201367 doi:https:\/\/doi.org\/10.1017\/9781108354882.005.","DOI":"10.1017\/9781108354882.005"},{"key":"85_CR5","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/S0140-6736(13)62227-8","volume":"383","author":"JPA Ioannidis","year":"2014","unstructured":"Ioannidis JPA, Greenland S, Hlatky MA, Khoury MJ, Macleod MR, Moher D, Schulz KF, Tibshirani R. Increasing value and reducing waste in research design, conduct, and analysis. Lancet. 2014;383:166\u201375.","journal-title":"Lancet"},{"issue":"5","key":"85_CR6","doi-asserted-by":"publisher","first-page":"368","DOI":"10.2174\/156652309789753392","volume":"9","author":"PR Lowenstein","year":"2009","unstructured":"Lowenstein PR, Castro MG. Uncertainty in the translation of preclinical experiments to clinical trials. Why do Most phase III clinical trials fail? Curr Gene Ther. 2009;9(5):368\u201374.","journal-title":"Curr Gene Ther"},{"issue":"11","key":"85_CR7","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1002\/mds.26010","volume":"29","author":"T Philips","year":"2014","unstructured":"Philips T, Rothstein JD, Pouladi MA. Preclinical models: Needed in translation? A Pro\/Con debate. Mov Disord. 2014;29(11):1391\u20136. https:\/\/doi.org\/10.1002\/mds.26010.","journal-title":"Mov Disord"},{"issue":"3","key":"85_CR8","doi-asserted-by":"publisher","first-page":"e1000245","DOI":"10.1371\/journal.pmed.1000245","volume":"7","author":"HB Van der Worp","year":"2010","unstructured":"Van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, et al. Can animal models of disease reliably inform human studies? PLoS Med. 2010;7(3):e1000245. https:\/\/doi.org\/10.1371\/journal.pmed.1000245.","journal-title":"PLoS Med"},{"key":"85_CR9","first-page":"422","volume":"3","author":"D Yu","year":"2011","unstructured":"Yu D. Translational research: current status, challenges and future strategies. Am J Transl Res. 2011;3:422\u201333.","journal-title":"Am J Transl Res"},{"key":"85_CR10","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/7854_2014_278","volume":"19","author":"P Droege","year":"2015","unstructured":"Droege P, Braithwaite VA. A framework for investigating animal consciousness. Curr Top Behav Neurosci. 2015;19:79\u201398.","journal-title":"Curr Top Behav Neurosci"},{"key":"85_CR11","volume-title":"The case of animal rights","author":"T Regan","year":"1983","unstructured":"Regan T. The case of animal rights. Berkeley: University of California Press; 1983."},{"key":"85_CR12","volume-title":"Animal rights and human morality","author":"BE Rollin","year":"1992","unstructured":"Rollin BE. Animal rights and human morality. New York: Prometheus Books; 1992."},{"key":"85_CR13","volume-title":"Moral status: obligations to persons and other living things","author":"MA Warren","year":"1997","unstructured":"Warren MA. Moral status: obligations to persons and other living things. Oxford: Clarendon; 1997."},{"key":"85_CR14","volume-title":"Animal liberation","author":"P Singer","year":"1990","unstructured":"Singer P. Animal liberation. New York: Random House; 1990."},{"key":"85_CR15","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511597961","volume-title":"The animals issue: moral theory in practice","author":"P Carruthers","year":"1992","unstructured":"Carruthers P. The animals issue: moral theory in practice. Cambridge: Cambridge UP; 1992."},{"key":"85_CR16","unstructured":"Dombrowski D. Babies and beasts: the argument from marginal cases. Champaign: University of Illinois Press; 1997."},{"issue":"2","key":"85_CR17","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/japp.12051","volume":"31","author":"O Horta","year":"2014","unstructured":"Horta O. The Scope of the Argument from Species Overlap. Journal of Applied Philosophy. 2014;31(2):142\u201354.","journal-title":"Journal of Applied Philosophy"},{"key":"85_CR18","doi-asserted-by":"publisher","DOI":"10.1017\/9781108354882","volume-title":"Animal ethics in animal research","author":"HM R\u00f6cklinsberg","year":"2017","unstructured":"R\u00f6cklinsberg HM, Gjerris M, Olsson IAS. Animal ethics in animal research. Cambridge: Cambridge University Press; 2017."},{"key":"85_CR19","volume-title":"The principles of humane experimental technique","author":"WMS Russell","year":"2013","unstructured":"Russell WMS, Burch RL. The principles of humane experimental technique. Baltimore: Johns Hopkins University; 2013."},{"issue":"1","key":"85_CR20","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1177\/0023677218783004","volume":"53","author":"Herwig Grimm","year":"2018","unstructured":"Grimm H, Olsson IAS, Sand\u00f8e P. Harm\u2013benefit analysis \u2013 what is the added value? A review of alternative strategies for weighing harms and benefits as part of the assessment of animal research, Lab Anim 2018. https:\/\/doi.org\/https:\/\/doi.org\/10.1177\/0023677218783004.","journal-title":"Laboratory Animals"},{"key":"85_CR21","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1136\/jme.2008.026989","volume":"35","author":"M Ideland","year":"2009","unstructured":"Ideland M. Different views on ethics: how animal ethics is situated in a committee culture. J Med Ethics. 2009;35:258\u201361.","journal-title":"J Med Ethics"},{"key":"85_CR22","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/BF02652653","volume":"33","author":"G Spielthenner","year":"2005","unstructured":"Spielthenner G. Consequentialism or deontology? Philosophia. 2005;33:217\u201335.","journal-title":"Philosophia"},{"key":"85_CR23","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s00213-003-1478-y","volume":"171","author":"JP Gluck","year":"2003","unstructured":"Gluck JP, Bell J. Ethical issues in the use of animals in biomedical and psychopharmocological research. Psychopharmacology. 2003;171:6\u201312.","journal-title":"Psychopharmacology"},{"key":"85_CR24","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1747-5341-4-2","volume":"4","author":"N Shanks","year":"2009","unstructured":"Shanks N, Greek R, Greek J. Are animal models predictive for humans? Philos Ethics Humanit Med. 2009;4:2.","journal-title":"Philos Ethics Humanit Med"},{"key":"85_CR25","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1747-5341-5-14","volume":"5","author":"R Greek","year":"2010","unstructured":"Greek R, Greek J. Is the use of sentient animals in basic research justifiable? Philos Ethics Humanit Med. 2010;5:14. https:\/\/doi.org\/10.1186\/1747-5341-5-14.","journal-title":"Philos Ethics Humanit Med"},{"key":"85_CR26","doi-asserted-by":"publisher","unstructured":"Leenaars CHC, Kouwenaar C, Stafleu FR, Bleich A, Ritskes-Hoitinga M, De Vries RBM, Meijboom FLB. Animal to human translation: a systematic scoping review of reported concordance rates. J Transl Med 2019; 17:223, https:\/\/doi.org\/https:\/\/doi.org\/10.1186\/s12967-019-1976-2.","DOI":"10.1186\/s12967-019-1976-2"},{"key":"85_CR27","doi-asserted-by":"publisher","first-page":"g3387.4","DOI":"10.1136\/bmj.g3387","volume":"348","author":"P Pound","year":"2014","unstructured":"Pound P, Bracken MB. Is animal research sufficiently evidence based to be a cornerstone of biomedical research? BMJ. 2014;348:g3387.4.","journal-title":"BMJ"},{"key":"85_CR28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1258\/002367707780378212","volume":"41","author":"JA Smith","year":"2007","unstructured":"Smith JA, Van den Broek FAR, Martorell JC, et al. Principles and practice in ethical review of animal experiments across Europe: summary of the report of a FELASA working group on ethical evaluation of animal experiments. Lab Anim. 2007;41:143\u201360.","journal-title":"Lab Anim"},{"key":"85_CR29","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1086\/287460","volume":"23","author":"HA Shepard","year":"1956","unstructured":"Shepard HA. Basic research and the social system of pure science. Philos Sci. 1956;23:48\u201357.","journal-title":"Philos Sci"},{"key":"85_CR30","unstructured":"Pritchard D, Turri J. The value of knowledge. in: The Stanford Encyclopedia of Philosophy (Winter 2012 Edition), Zalta, E.N. (Ed.) 2012. http:\/\/plato.stanford.edu\/archives\/win2012\/entries\/knowledge-value\/"},{"key":"85_CR31","first-page":"47","volume-title":"Biological psychiatry","author":"M Sarter","year":"2002","unstructured":"Sarter M, Bruno JP. Animal models in biological psychiatry. In: D'Haenen H, den Boer JA, Willner P, editors. Biological psychiatry. Chichester: Wiley; 2002. p. 47\u201379."},{"key":"85_CR32","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.brainresrev.2006.01.006","volume":"52","author":"FJ Van der Staay","year":"2006","unstructured":"Van der Staay FJ. Animal models of behavioral dysfunctions: basic concepts and classifications, and an evaluation strategy. Brain Res Rev. 2006;52:131\u201359.","journal-title":"Brain Res Rev"},{"key":"85_CR33","volume-title":"Brute Science: Dilemmas of Animal Experimentation","author":"H LaFollette","year":"1996","unstructured":"LaFollette H, Shanks N. Brute Science: Dilemmas of Animal Experimentation. New York: Routedge; 1996."},{"key":"85_CR34","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1037\/0735-7028.31.1.5","volume":"31","author":"D Satcher","year":"2000","unstructured":"Satcher D. Mental health: a report of the surgeon general--executive summary. Prof Psychol Res Pract. 2000;31:5\u201313.","journal-title":"Prof Psychol Res Pract"},{"key":"85_CR35","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/1741-7015-11-126","volume":"11","author":"BN Cuthbert","year":"2013","unstructured":"Cuthbert BN, Insel TR. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med. 2013;11:126. https:\/\/doi.org\/10.1186\/1741-7015-11-126.","journal-title":"BMC Med"},{"issue":"2","key":"85_CR36","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1017\/S0963180113000674","volume":"23","author":"MD Rollin","year":"2014","unstructured":"Rollin MD, Rollin BE. Crazy like a fox. Validity and ethics of animal models of human psychiatric disease. Camb Q Healthc Ethics. 2014;23(2):140\u201351. https:\/\/doi.org\/10.1017\/S0963180113000674.","journal-title":"Camb Q Healthc Ethics"},{"key":"85_CR37","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1146\/annurev.clinpsy.3.022806.091532","volume":"6","author":"SE Hyman","year":"2010","unstructured":"Hyman SE. The diagnosis of mental disorders: the problem of reification. Annu Rev Clin Psychol. 2010;6:155\u201379.","journal-title":"Annu Rev Clin Psychol"},{"key":"85_CR38","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1038\/nn.2647","volume":"13","author":"EJ Nestler","year":"2010","unstructured":"Nestler EJ, Hyman SE. Animal models of neuropsychiatric disorders. Nat Neurosci. 2010;13:1161\u20139. https:\/\/doi.org\/10.1038\/nn.2647.","journal-title":"Nat Neurosci"},{"issue":"2","key":"85_CR39","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0304-3940(99)00840-X","volume":"277","author":"JA Ihalainen","year":"1999","unstructured":"Ihalainen JA, Riekkinen P Jr, Feenstra MG. Comparison of dopamine and noradrenaline release in mouse prefrontal cortex, striatum and hippocampus using microdialysis. Neurosci Lett. 1999;277(2):71\u20134.","journal-title":"Neurosci Lett"},{"key":"85_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.5334\/jcr.174","volume":"17","author":"JML Menon","year":"2019","unstructured":"Menon JML, Nolten C, et al. Brain microdialysate monoamines in relation to circadian rhythms, sleep, and sleep deprivation - a systematic review, network meta-analysis, and new primary data. J Circadian Rhythms. 2019;17:1. https:\/\/doi.org\/10.5334\/jcr.174.","journal-title":"J Circadian Rhythms"},{"key":"85_CR41","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2460\/javma.235.4.363","volume":"235","author":"J Greek","year":"2009","unstructured":"Greek J, Shanks N. Thoughts on animal models for human disease and treatment. J Am Vet Med Assoc. 2009;235:363. https:\/\/doi.org\/10.2460\/javma.235.4.363.","journal-title":"J Am Vet Med Assoc"},{"key":"85_CR42","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1742-4682-9-40","volume":"9","author":"R Greek","year":"2012","unstructured":"Greek R, Rice MJ. Animal models and conserved processes. Theor Biol Med Model. 2012;9:40.","journal-title":"Theor Biol Med Model"},{"key":"85_CR43","first-page":"787","volume-title":"Psychopharmacology: the fourth generation of progress","author":"MA Geyer","year":"1995","unstructured":"Geyer MA, Markou A. Animal models of psychiatric disorders. In: Bloom FE, Kupfer DJ, editors. Psychopharmacology: the fourth generation of progress. New York: Raven; 1995. p. 787\u201398."},{"key":"85_CR44","volume-title":"The Philosophical Review","author":"T Nagel","year":"1974","unstructured":"Nagel T. What is it like to be a bat? In: The Philosophical Review; 1974."},{"key":"85_CR45","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1006\/anbe.1998.0836","volume":"56","author":"CM Sherwin","year":"1998","unstructured":"Sherwin CM. Voluntary wheel running: a review and novel interpretation. Anim Behav. 1998;56:11\u201327.","journal-title":"Anim Behav"},{"key":"85_CR46","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6799-0","volume-title":"Risk governance: coping with uncertainty in a complex world","author":"O Renn","year":"2008","unstructured":"Renn O. Risk governance: coping with uncertainty in a complex world. London: Earthscan; 2008."},{"key":"85_CR47","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/npp.2008.173","volume":"34","author":"A Markou","year":"2009","unstructured":"Markou A, Chiamulera C, Geyer MA, et al. Removing obstacles in neuroscience drug discovery: the future path for animal models. Neuropsychopharmacology. 2009;34:74\u201389. https:\/\/doi.org\/10.1038\/npp.2008.173.","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"85_CR48","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/gbb.12091","volume":"13","author":"E Kostrzewa","year":"2014","unstructured":"Kostrzewa E, Kas MJ. The use of mouse models to unravel genetic architecture of physical activity: a review. Genes Brain Behav. 2014;13(1):87\u2013103. https:\/\/doi.org\/10.1111\/gbb.12091.","journal-title":"Genes Brain Behav"},{"issue":"20","key":"85_CR49","doi-asserted-by":"publisher","first-page":"4767","DOI":"10.1111\/bph.12789","volume":"171","author":"MA van Gestel","year":"2014","unstructured":"van Gestel MA, Kostrzewa E, Adan RA, Janhunen SK. Pharmacological manipulations in animal models of anorexia and binge eating in relation to humans. Br J Pharmacol. 2014;171(20):4767\u201384. https:\/\/doi.org\/10.1111\/bph.12789.","journal-title":"Br J Pharmacol"},{"key":"85_CR50","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1002\/erv.630","volume":"13","author":"T Hechle","year":"2005","unstructured":"Hechle T, Beumont P, Marks P, Touyz S. How do clinical specialists understand the role of physical activity in eating disorders? Eur Eat Disord Rev. 2005;13:125\u201332.","journal-title":"Eur Eat Disord Rev"},{"key":"85_CR51","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1249\/MSS.0b013e31828e8f07","volume":"45","author":"M Alberti","year":"2013","unstructured":"Alberti M, Galvani C, El GM, et al. Assessment of physical activity in anorexia nervosa and treatment outcome. Med Sci Sports Exerc. 2013;45:1643\u20138. https:\/\/doi.org\/10.1249\/MSS.0b013e31828e8f07.","journal-title":"Med Sci Sports Exerc"},{"key":"85_CR52","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1002\/1098-108X(199401)15:1<21::AID-EAT2260150104>3.0.CO;2-K","volume":"15","author":"PJ Beumont","year":"1994","unstructured":"Beumont PJ, Arthur B, Russell JD, Touyz SW. Excessive physical activity in dieting disorder patients: proposals for a supervised exercise program. Int J Eat Disord. 1994;15:21\u201336.","journal-title":"Int J Eat Disord"},{"key":"85_CR53","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1017\/S0033291700029044","volume":"24","author":"C Davis","year":"1994","unstructured":"Davis C, Kennedy SH, Ravelski E, Dionne M. The role of physical activity in the development and maintenance of eating disorders. Psychol Med. 1994;24:957\u201367.","journal-title":"Psychol Med"},{"key":"85_CR54","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1002\/eat.20214","volume":"39","author":"JM Mond","year":"2006","unstructured":"Mond JM, Hay PJ, Rodgers B, Owen C. An update on the definition of \u201cexcessive exercise\u201d in eating disorders research. Int J Eat Disord. 2006;39:147\u201353.","journal-title":"Int J Eat Disord"},{"key":"85_CR55","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC: American Psychiatric Association Publishing; 2013.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"85_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2050-2974-1-16","volume":"2","author":"S Young","year":"2013","unstructured":"Young S, Rhodes P, Touyz S, Hay P. The relationship between obsessive-compulsive personality disorder traits, obsessive-compulsive disorder and excessive exercise in patients with anorexia nervosa: a systematic review. J Eat Disord. 2013;2:1\u201316. https:\/\/doi.org\/10.1186\/2050-2974-1-16.","journal-title":"J Eat Disord"},{"key":"85_CR57","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1002\/eat.20753","volume":"43","author":"S Bratland-Sanda","year":"2010","unstructured":"Bratland-Sanda S, Sundgot-Borgen J, \u00d8yvind R, et al. \u201cI\u2019m not physically active - I only go for walks\u201d: physical activity in patients with longstanding eating disorders. Int J Eat Disord. 2010;43:88\u201392. https:\/\/doi.org\/10.1002\/eat.20753.","journal-title":"Int J Eat Disord"},{"key":"85_CR58","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1111\/j.1442-200x.2005.02072.x","volume":"47","author":"K Inoko","year":"2005","unstructured":"Inoko K, Nishizono-Maher A, Ishii K, Osawa M. Effect of medical treatments on psychiatric symptoms in children with anorexia nervosa. Pediatr Int. 2005;47:326\u20138.","journal-title":"Pediatr Int"},{"key":"85_CR59","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/0010-440X(78)90072-X","volume":"19","author":"L Kron","year":"1978","unstructured":"Kron L, Katz JL, Gorzynski G, Weiner H. Hyperactivity in anorexia-nervosa - fundamental clinical feature. Compr Psychiatry. 1978;19:433\u201340.","journal-title":"Compr Psychiatry"},{"key":"85_CR60","volume-title":"Solving the anorexia puzzle - a scientific approach","author":"WF Epling","year":"1992","unstructured":"Epling WF, Pierce WD. Solving the anorexia puzzle - a scientific approach. Toronto: Hogrefe & Huber; 1992."},{"key":"85_CR61","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1002\/eat.20035","volume":"36","author":"K Holtkamp","year":"2004","unstructured":"Holtkamp K, Hebebrand J, Herpertz-Dahlmann B. The contribution of anxiety and food restriction on physical activity levels in acute anorexia nervosa. Int J Eat Disord. 2004;36:163\u201371.","journal-title":"Int J Eat Disord"},{"key":"85_CR62","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/BF03392649","volume":"17","author":"WD Pierce","year":"1994","unstructured":"Pierce WD, Epling WF, Dews PB, et al. Activity anorexia: an interplay between basic and applied behavior analysis. Behav Anal. 1994;17:7\u201323.","journal-title":"Behav Anal"},{"key":"85_CR63","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/j.yhbeh.2006.06.030","volume":"50","author":"P Sodersten","year":"2006","unstructured":"Sodersten P, Bergh C, Zandian M. Understanding eating disorders. Horm Behav. 2006;50:572\u20138.","journal-title":"Horm Behav"},{"key":"85_CR64","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1007\/s00213-008-1102-2","volume":"199","author":"RC Casper","year":"2008","unstructured":"Casper RC, Sullivan EL, Tecott L. Relevance of animal models to human eating disorders and obesity. Psychopharmacology. 2008;199:313\u201329. https:\/\/doi.org\/10.1007\/s00213-008-1102-2.","journal-title":"Psychopharmacology"},{"key":"85_CR65","unstructured":"Rieg TS. Validity criteria for animal models of anorexia nervosa involving activity. In: Epling WF, Pierce WD, editors. Activity Anorexia: Theory, Research, and Treatment: Psychology Press; 2013."},{"key":"85_CR66","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1002\/eat.22095","volume":"46","author":"E Gutierrez","year":"2013","unstructured":"Gutierrez E. A rat in the labyrinth of anorexia nervosa: contributions of the activity-based anorexia rodent model to the understanding of anorexia nervosa. Int J Eat Disord. 2013;46:289\u2013301. https:\/\/doi.org\/10.1002\/eat.22095.","journal-title":"Int J Eat Disord."},{"key":"85_CR67","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.biopsych.2005.11.001","volume":"60","author":"K Holtkamp","year":"2006","unstructured":"Holtkamp K, Herpertz-Dahlmann B, Hebebrand K, et al. Physical activity and restlessness correlate with leptin levels in patients with adolescent anorexia nervosa. Biol Psychiatry. 2006;60:311\u20133.","journal-title":"Biol Psychiatry"},{"key":"85_CR68","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/sj.mp.4000771","volume":"5","author":"C Exner","year":"2000","unstructured":"Exner C, Hebebrand J, Remschmidt H, et al. Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa. Mol Psychiatry. 2000;5:476\u201381.","journal-title":"Mol Psychiatry"},{"key":"85_CR69","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.biopsych.2005.03.011","volume":"58","author":"J Hillebrand","year":"2005","unstructured":"Hillebrand J, Koeners M, Derijke C, et al. Leptin treatment in activity-based anorexia. Biol Psychiatry. 2005;58:165\u201371.","journal-title":"Biol Psychiatry"},{"key":"85_CR70","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1007\/s00702-007-0740-6","volume":"114","author":"AA Van Elburg","year":"2007","unstructured":"Van Elburg AA, Kas MJ, Hillebrand JJ, et al. The impact of hyperactivity and leptin on recovery from anorexia nervosa. J Neural Transm. 2007;114:1233\u20137.","journal-title":"J Neural Transm"},{"key":"85_CR71","doi-asserted-by":"publisher","first-page":"116278","DOI":"10.1016\/j.neuroimage.2019.116278","volume":"205","author":"J Grandjean","year":"2019","unstructured":"Grandjean J, Canella C, et al. Common functional networks in the mouse brain revealed by multi-Centre resting-state fMRI analysis. Neuroimage. 2019;205:116278. https:\/\/doi.org\/10.1016\/j.neuroimage.2019.116278.","journal-title":"Neuroimage"},{"key":"85_CR72","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1258\/jrsm.2008.080087","volume":"101","author":"S Green","year":"2008","unstructured":"Green S. Medical progress depends on animal models-doesn\u2019t it? J R Soc Med. 2008;101:220\u20131.","journal-title":"J R Soc Med"},{"issue":"7","key":"85_CR73","doi-asserted-by":"publisher","first-page":"e1001482","DOI":"10.1371\/journal.pmed.1001482","volume":"10","author":"CR Hooijmans","year":"2013","unstructured":"Hooijmans CR, Ritskes-Hoitinga M. Progress in using systematic reviews of animal studies to improve translational research. PLoS Med. 2013;10(7):e1001482.","journal-title":"PLoS Med"},{"issue":"7","key":"85_CR74","doi-asserted-by":"publisher","first-page":"e1001489","DOI":"10.1371\/journal.pmed.1001489","volume":"10","author":"VC Henderson","year":"2013","unstructured":"Henderson VC, Kimmelman J, Fergusson D, Grimshaw JM, Hackam DG. Threats to validity in the design and conduct of preclinical efficacy studies: a systematic review of guidelines for in vivo animal experiments. PLoS Med. 2013;10(7):e1001489 Epub 2013\/08\/13. pmid:23935460.","journal-title":"PLoS Med"},{"key":"85_CR75","doi-asserted-by":"publisher","first-page":"275","DOI":"10.14573\/altex.2013.3.275","volume":"30","author":"T Hartung","year":"2013","unstructured":"Hartung T. Food for thought look Back in anger \u2013 what clinical studies tell us about preclinical work. ALTEX. 2013;30:275\u201391.","journal-title":"ALTEX"},{"issue":"2","key":"85_CR76","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1258\/jrsm.2007.070164","volume":"101","author":"RA Matthews","year":"2008","unstructured":"Matthews RA. Medical progress depends on animal models - doesn't it? J R Soc Med. 2008;101(2):95\u20138. https:\/\/doi.org\/10.1258\/jrsm.2007.070164.","journal-title":"J R Soc Med"},{"key":"85_CR77","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1471-2288-6-10","volume":"6","author":"LE Mignini","year":"2006","unstructured":"Mignini LE, Khan KS. Methodological quality of systematic reviews of animal studies: a survey of reviews of basic research. BMC Med Res Methodol. 2006;6:10.","journal-title":"BMC Med Res Methodol"},{"key":"85_CR78","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/S0140-6736(02)09812-4","volume":"360","author":"P Sandercock","year":"2002","unstructured":"Sandercock P, Roberts I. Systematic reviews of animal experiments. Lancet. 2002;360:586.","journal-title":"Lancet"},{"key":"85_CR79","unstructured":"Stafleu FR, Leenaars CHC, Coenen de Roo CJJ, Ritskes-Hoitinga M, Meijboom FLB. The translation-standardisation paradox: Translational strategies to tackle it New horizons in translational medicine 2016; 3: 96."},{"issue":"1","key":"85_CR80","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/YCO.0b013e3280117733","volume":"20","author":"JF Cryan","year":"2007","unstructured":"Cryan JF, Slattery DA. Animal models of mood disorders: recent developments. Curr Opin Psychiatry. 2007;20(1):1\u20137.","journal-title":"Curr Opin Psychiatry"},{"key":"85_CR81","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1162\/posc.1999.7.1.87","volume":"7","author":"J Burkhardt","year":"1999","unstructured":"Burkhardt J. Scientific values and moral education in the teaching of science. Perspect Sci. 1999;7:87\u2013110.","journal-title":"Perspect Sci"},{"issue":"6","key":"85_CR82","doi-asserted-by":"publisher","first-page":"e2006343","DOI":"10.1371\/journal.pbio.2006343","volume":"16","author":"Mark Yarborough","year":"2018","unstructured":"Yarborough M, Bredenoord A, D\u2019Abramo F, Joyce NC, Kimmelman J, Ogbogu, U, Sena, E., Strech, D., Dirnagl U. The bench is closer to the bedside than we think: Uncovering the ethical ties between preclinical researchers in translational neuroscience and patients in clinical trials. PLOS Biology, 2018; 16\/6: e2006343. https:\/\/doi.org\/https:\/\/doi.org\/10.1371\/journal.pbio.2006343.","journal-title":"PLOS Biology"},{"issue":"3","key":"85_CR83","doi-asserted-by":"publisher","first-page":"e1001010","DOI":"10.1371\/journal.pmed.1001010","volume":"8","author":"Jonathan Kimmelman","year":"2011","unstructured":"Kimmelman J, London AJ. Predicting harms and benefits in translational trials: ethics, evidence, and uncertainty. PLoS Med 2011; 8(3): e1001010. https:\/\/doi.org\/https:\/\/doi.org\/10.1371\/journal.pmed.1001010.","journal-title":"PLoS Medicine"},{"key":"85_CR84","doi-asserted-by":"crossref","first-page":"S121","DOI":"10.1017\/S0962728600014469","volume":"13","author":"P Sand\u00f8e","year":"2004","unstructured":"Sand\u00f8e P, Forkman B, Christiansen SB. Scientific uncertainty - how should it be handled in relation to scientific advice regarding animal welfare issues? Anim Welf. 2004;13:S121\u20136.","journal-title":"Anim Welf"}],"container-title":["Philosophy, Ethics, and Humanities in Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13010-019-0085-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13010-019-0085-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13010-019-0085-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T14:16:49Z","timestamp":1695651409000},"score":1,"resource":{"primary":{"URL":"https:\/\/peh-med.biomedcentral.com\/articles\/10.1186\/s13010-019-0085-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,23]]},"references-count":84,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["85"],"URL":"https:\/\/doi.org\/10.1186\/s13010-019-0085-4","relation":{},"ISSN":["1747-5341"],"issn-type":[{"type":"electronic","value":"1747-5341"}],"subject":[],"published":{"date-parts":[[2020,1,23]]},"assertion":[{"value":"15 August 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}