Behavioural Brain Research 265 (2014) 53–60 Contents lists available at ScienceDirect Behavioural Brain Research jou rn al hom epage: www.elsevier.com/locate/bbr Research report NK 1 receptors antagonism of dorsal hippocampus counteract the anxiogenic-like effects induced by pilocarpine in non-convulsive Wistar rats Filipe Silveira Duarte a , Alexandre Ademar Hoeller b,f , Marcelo Duzzioni c , Elaine Cristina Gavioli d , Newton Sabino Canteras e , Thereza Christina Monteiro De Lima f,∗ a Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, PE 50670-901, Brazil b Postgraduate Program in Medical Science, Center of Health Sciences, University Hospital, Federal University of Santa Catarina, Florianópolis, SC 88040-970, Brazil c Institute of Biological Sciences and Health, Federal University of Alagoas, Maceió, AL 57020-720, Brazil d Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte, Natal, RN 59072-970, Brazil e Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil f Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Florianópolis, SC 88049-900, Brazil h i g h l i g h t s • NK 1 receptor antagonist’s FK888 did not alter emotional responses in CA 1 or LSD. • Infusion of FK888 into CA 1 inhibits long-term anxiogenic responses induced by PILO. • PILO changes anxiogenic responses modulated by SP-NK 1 receptor signaling in CA 1 . a r t i c l e i n f o Article history: Received 3 October 2013 Received in revised form 28 January 2014 Accepted 31 January 2014 Available online 7 February 2014 Keywords: Pilocarpine Anxiety NK1 receptor Dorsal hippocampus Lateral septum Elevated plus-maze a b s t r a c t Recent evidence supports a role for the substance P (SP) in the control of anxiety and epilepsy disorders. Aversive stimuli alter SP levels and SP immunoreactivity in limbic regions, suggesting that changes in SP-NK 1 receptor signaling may modulate the neuronal excitability involved in seizures and anxiogenesis. The involvement of NK 1 receptors of the dorsal hippocampus and lateral septum in the anxiogenic-like effects induced by a single injection of pilocarpine (PILO) was examined in non-convulsive rats evaluated in the elevated plus-maze (EPM). Male Wistar rats were systemically injected with methyl-scopolamine (1 mg/kg) followed 30 min later by saline or PILO (350 mg/kg) and only rats that did not present status epilepticus were used. One month later, vehicle or FK888 (100 pmol) – an NK 1 receptor antagonist – were infused in the dorsal hippocampus or the lateral septum of the rats and then behaviorally evaluated in the EPM. Previous treatment with PILO decreased the time spent in and the frequency of entries in the open arms of the EPM, besides altering risk-assessment behaviors such as the number of unprotected head- dipping, protected stretch-attend postures and the frequency of open-arms end activity, showing thus a long-lasting anxiogenic-like profile. FK888 did not show any effect per se but inhibited the anxiogenic responses induced by PILO when injected into the dorsal hippocampus, but not into the lateral septum. Our data suggest that SP-NK 1 receptor signaling of the dorsal hippocampus is involved in the anxiogenic- like profile induced by PILO in rats evaluated in the EPM test. © 2014 Elsevier B.V. All rights reserved. ∗ Corresponding author at: Department of Pharmacology, Center of Biological Sciences, Federal University of Santa Catarina, Campus Universitario, Trindade, Flo- rianopolis, SC 88049-900, Brazil. Tel.: +55 48 3721 9491x225/3721 2476; fax: +55 48 3721 9813. E-mail addresses: thereza.lima@ufsc.br, t de lima@hotmail.com (T.C.M. De Lima). 1. Introduction Depression and anxiety disorders are major comorbidities in epilepsy [1–6]. Several animal models demonstrated that the sta- tus epilepticus (SE) observed in epileptic animals induces aggressive, depressive and anxiety-like behaviors [7–14] supporting the exist- ence of a shared causation of epilepsy and affective disorders. 0166-4328/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.bbr.2014.01.050