Behavioural Brain Research 300 (2016) 160–174 Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Multiple rodent models and behavioral measures reveal unexpected responses to FTY720 and DMF in experimental autoimmune encephalomyelitis N.M.W.J. de Bruin a,∗ , K. Schmitz b , S. Schiffmann a , N. Tafferner a , M. Schmidt a , H. Jordan a , A. Häußler b , I. Tegeder b , G. Geisslinger a,b , M.J. Parnham a a Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany b Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe-University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany h i g h l i g h t s • Deficits in motor functions and sociability were observed during score-free intervals in immunized SJL/J mice. • Neither prophylactic nor late-therapeutic treatment with FTY720 reduced clinical scores or reversed deficits in the rotarod test in immunized SJL/J mice. • Prophylactic treatment with FTY720 improved the gait of SJL/J mice. • Late-therapeutic treatment with FTY-720 improved manifestations of reduced social (re)cognition or preference for social novelty. • Improvements in behavioral deficits can occur in absence of clinical scores. a r t i c l e i n f o Article history: Received 4 November 2015 Received in revised form 30 November 2015 Accepted 9 December 2015 Available online 12 December 2015 Keywords: Experimental autoimmune encephalomyelitis Multiple sclerosis FTY720 Social novelty test Fumarate Gait analysis a b s t r a c t Experimental autoimmune encephalomyelitis (EAE) is a widely-used rodent model for multiple sclerosis (MS), but a single model can hardly capture all features of MS. We investigated whether behavioral parameters in addition to clinical motor function scores could be used to assess treatment efficacy during score-free intervals in the relapsing-remitting EAE model in SJL/J mice. We studied the effects of the clinical reference compounds FTY720 (fingolimod, 0.5 mg/kg/day) and dimethyl fumarate (DMF, 20–30 mg/kg/day) on clinical scores in several rodent EAE models in order to generate efficacy profiles. SJL/J mice with relapsing-remitting EAE were studied using behavioral tests, including rotarod, gait analy- sis, locomotor activity and grip strength. SJL/J mice were also examined according to Crawley’s sociability and preference for social novelty test. Prophylactic treatment with FTY720 prevented clinical scores in three of the four EAE rodent models: Dark Agouti (DA) and Lewis rats and C57BL/6J mice. Neither pro- phylactic nor late-therapeutic treatment with FTY720 reduced clinical scores or reversed deficits in the rotarod test in SJL/J mice, but we observed effects on motor functions and sociability in the absence of clin- ical scores. Prophylactic treatment with FTY720 improved the gait of SJL/J mice whereas late-therapeutic treatment improved manifestations of reduced social (re)cognition or preference for social novelty. DMF was tested in three EAE models and did not improve clinical scores at the dose used. These data indicate that improvements in behavioral deficits can occur in absence of clinical scores, which indicate subtle drug effects and may have translational value for human MS. © 2015 Elsevier B.V. All rights reserved. ∗ Corresponding author. Fax: +49 69 6301 7636. E-mail addresses: natasja.debruin@gmail.com, natasja.debruin@ime.fraunhofer.de (N.M.W.J. de Bruin). 1. Introduction Experimental autoimmune encephalomyelitis (EAE) is a widely- used rodent model for multiple sclerosis (MS), but a single model can hardly capture and adequately incorporate all features of MS [1]. A number of different EAE models are available, resulting in different disease-progression patterns and clinical features [1–3] http://dx.doi.org/10.1016/j.bbr.2015.12.006 0166-4328/© 2015 Elsevier B.V. All rights reserved.