Abstract. Introduction. R.N. Takahashi 1, O. Berton 2,3, P. Mormède 2 and F. Chaouloff 2

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1 Brazilian Journal of Medical and Biological Research (21) 34: Effects of diazepam and SB in SHR and Lewis rats ISSN 1-879X 675 Strain-dependent effects of diazepam and the 5-HT 2B/2C receptor antagonist SB in spontaneously hypertensive and Lewis rats tested in the elevated plus-maze R.N. Takahashi 1, O. Berton 2,3, P. Mormède 2 and F. Chaouloff 2 1 Departamento de Farmacologia, Universidade Federal de Santa Catarina, Florianópolis, SC, Brasil 2 NeuroGénétique et Stress, INSERM U471-INRA, Bordeaux, France 3 UCB Pharma, Preclinical CNS Research, Braine-L Alleud, Belgium Correspondence R.N. Takahashi Departamento de Farmacologia, UFSC R. Ferreira Lima, Florianópolis, SC Brasil Fax: takahashi@farmaco.ufsc.br Presented at the XIII Annual Meeting of the Federação de Sociedades de Biologia Experimental, Caxambu, MG, Brazil, August 26-29, Received September 15, 2 Accepted February 5, 21 Abstract Key words Anxiety Diazepam Elevated plus-maze Lewis rats Spontaneously hypertensive rats Locomotor activity m-chlorophenylpiperazine SB Introduction Braz J Med Biol Res 34(5) 21

2 676 R.N. Takahashi et al. Material and Methods Subjects Procedure Braz J Med Biol Res 34(5) 21

3 Effects of diazepam and SB in SHR and Lewis rats 677 Material Statistical analysis Results Behavioral effects of diazepam Behavioral effects of SB Braz J Med Biol Res 34(5) 21

4 678 R.N. Takahashi et al. Discussion Figure 1 - Effects of diazepam administered ip (3 min before testing) in Lewis (LEW) and spontaneously hypertensive rats (SHR) tested for 5 min in the elevated plus-maze. Results are reported as the mean ± SEM for 9-1 rats. + P<.5 for the interstrain difference between vehicle-treated rats (Tukey test). P<.5, at least for the effects of diazepam against vehicle (Dunn or Tukey test). Open arm entries (%) LEW SHR Time in open arms (%) Closed arm entries Total arm entries Diazepam (mg/kg) Diazepam (mg/kg) Braz J Med Biol Res 34(5) 21

5 Effects of diazepam and SB in SHR and Lewis rats 679 Open arm entries (%) LEW SHR Time in open arms (%) Figure 2 - Effects of SB administered ip (3 min before testing) in Lewis (LEW) and spontaneously hypertensive rats (SHR) tested for 5 min in the elevated plus-maze. Results are reported as the mean ± SEM for 6-1 rats. + P<.5 for the interstrain difference between vehicle-treated rats (Dunn or Tukey test). P<.5, at least for the effects of SB against vehicle (Tukey test) Closed arm entries Total arm entries SB (mg/kg) SB (mg/kg) Beam breaks LEW SHR.9% NaCl mcpp (1.5 mg/kg) Figure 3 - Effects of m-chlorophenylpiperazine (mcpp) and saline administered ip on vehicle- and SB pretreated Lewis (LEW) and spontaneously hypertensive rats (SHR) 2 min before testing in activity cages for 15 min. These animals were immediately injected with saline or mcpp after completion of the plus-maze test (same rats as in Figure 2). Results are reported as the mean ± SEM for 6-1 rats. + P<.5 for the interstrain difference between vehicle-pretreated (mcppinjected) rats (Tukey test). P<.5, at least for the difference from vehicle-pretreated (saline-injected) rats (Tukey test) SB (mg/kg) Braz J Med Biol Res 34(5) 21

6 68 R.N. Takahashi et al. Braz J Med Biol Res 34(5) 21

7 Effects of diazepam and SB in SHR and Lewis rats 681 Acknowledgments References 1. Whitton P & Curzon G (199). Anxiogeniclike effect of infusing 1-(3-chlorophenyl) piperazine (mcpp) into the hippocampus. Psychopharmacology, 1: Kennett GA (1993). 5-HT 1C receptors and their therapeutic relevance. Current Opinion in Investigation Drugs, 2: Kennett GA (1992). 5-HT 1C receptor antagonists have anxiolytic-like actions in the rat social interaction model. Psychopharmacology, 17: Kennett GA, Pittaway K & Blackburn TP (1994). Evidence that 5-HT 2C receptor antagonists are anxiolytic in the rat Geller- Seifter model of anxiety. Psychopharmacology, 114: Forbes IT, Kennett GA, Gadre A, Ham P, Hayward CJ, Martin RT, Thompson M, Wood MD, Baxter GS, Glen A, Murphy OE, Stewart B & Blackburn TP (1993). N- (1-Methyl-5-indolyl)-N -(3-pyridyl)urea hydrochloride: the first selective 5-HT 1C receptor antagonist. Journal of Medicinal Chemistry, 36: Kennett GA, Bailey F, Piper DC & Blackburn TP (1995). Effect of SB 2646A, a 5-HT 2C /5-HT 2B receptor antagonist, in two conflict models of anxiety. Psychopharmacology, 118: Kennett GA, Wood MD, Bright F, Cilia J, Piper DC, Gager T, Thomas D, Baxter GS, Forbes IT, Ham P & Blackburn TP (1996). In vitro and in vivo profile of SB 26553, a potent 5-HT 2C /5-HT 2B receptor antagonist with anxiolytic-like properties. British Journal of Pharmacology, 117: Griebel G, Perrault G & Sanger DJ (1997). A comparative study of the effects of selective and non-selective 5-HT 2 receptor subtype antagonists in rat and mouse models of anxiety. Neuropharmacology, 36: Kennett GA & Curzon G (1988). Evidence that mcpp may have behavioral effects mediated by 5-HT 1C receptors. British Journal of Pharmacology, 94: Kulikov A, Aguerre S, Berton O, Ramos A, Mormède P & Chaouloff F (1997). Central serotonergic systems in the spontaneously hypertensive and Lewis rat strains that differ in the elevated plus-maze test of anxiety. Journal of Pharmacology and Experimental Therapeutics, 281: Pellow S, Chopin P, File SE & Briley M (1985). Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. Journal of Neuroscience Methods, 14: Ramos A, Berton O, Mormède P & Chaouloff F (1997). A multiple-test study of anxiety-related behaviours in six inbred rat strains. Behavioural Brain Research, 85: File SE (1991). The biological basis of anxiety. In: Meltzer HY & Nerozzi D (Editors), Current Practices and Future Developments in the Pharmacotherapy of Mental Disorders. Elsevier, Amsterdam, The Netherlands, Braz J Med Biol Res 34(5) 21

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