Putrescine produces antidepressant-like effects in the forced swimming test and in the tail suspension test in mice Andrea D.E. Zomkowski a , Adair Roberto S. Santos b , Ana Lúcia S. Rodrigues a, ⁎ a Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil b Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC 88040-900, Brazil Received 12 January 2006; received in revised form 27 April 2006; accepted 23 May 2006 Available online 5 July 2006 Abstract Putrescine, a polyamine present at high concentrations in the mammalian brain, was suggested to play a role in the modulation of depression. Thus, this study investigated the effect of putrescine in the mouse forced swimming test (FST) and in the tail suspension test (TST), two models predictive of antidepressant activity. Putrescine significantly reduced the immobility time both in the FST and in the TST (dose range of 1–10 mg/kg, i.p.), without changing locomotion in an open-field. I.c.v. injection of putrescine (0.1–10 nmol/site) also reduced the immobility time in the FST and in the TST. The pretreatment of mice with arcaine (1 mg/kg, i.p., an antagonist of the polyamine-site of NMDA receptor) completely blocked the anti-immobility effect of putrescine (10 mg/kg, i.p.). A subeffective dose of putrescine (0.1 mg/kg, i.p.) produced a synergistic antidepressant-like effect with agmatine (0.001 mg/kg, i.p.) in the FST. Moreover, a subeffective dose of putrescine (0.01 nmol/site, i.c.v.) produced a synergistic antidepressant-like effect with arcaine (50 μg/site, i.c.v.). The results indicate that putrescine produces antidepressant-like effects in the FST that seems to be mediated through its interaction with the polyamine-site of NMDA receptors. © 2006 Elsevier Inc. All rights reserved. Keywords: Depression; Forced swimming test; Polyamines; Putrescine; Tail suspension test 1. Introduction Polyamines (putrescine, spermidine and spermine) are organic cations of low molecular weight, present at high concentrations in the mammalian brain. They have important roles in cellular growth, cell differentiation, modulation of enzyme activities, regulation of ion channels and in the control of DNA and protein synthesis (Williams, 1997a; Hillary and Pegg, 2003; Moinard et al., 2005). Several biological functions for the polyamines have been reported including modulation of learning and memory (Rubin et al., 2000, 2001, 2004) and antinociceptive (Genedani et al., 1984; Kolhekar et al., 1994), neuroprotective (Adibhatla et al., 2002; Clarkson et al., 2004), and antioxidant (Bellé et al., 2004) properties. Putrescine is formed from ornithine in a reaction catalyzed by ornithine decarboxylase (ODC) and converted to spermidine by a specific synthase which utilizes decarboxilated S-adenosyl methionine as a propylamine donor; a spermine synthase converts spermidine to spermine (Williams, 1997a; Hillary and Pegg, 2003; Moinard et al., 2005). Putrescine may also be synthesized from agmatine by agmatinase in microorganisms and mammals (Hillary and Pegg, 2003). Polyamines have been shown to interact with different types of ion channels. These interactions include the effects of polyamines on NMDA receptors, which are involved in a variety of physiological processes in the central nervous system including the generation of long term potentiation, neuronal development and neuronal plasticity (Williams, 1997a). A growing amount of evidence has shown that the NMDA receptor is also involved in the pathogenesis of depression, since preclinical and clinical data have demonstrated that Progress in Neuro-Psychopharmacology & Biological Psychiatry 30 (2006) 1419 – 1425 www.elsevier.com/locate/pnpbp Abbreviations: DET, diethylenetriamine; FST, forced swimming test; i.c.v., intracerebroventricular; NMDA, N-methyl-D-aspartate receptors; NOS, nitric oxide synthase; ODC, ornithine decarboxylase; TST, tail suspension test. ⁎ Corresponding author. Tel.: +55 48 3331 5043; fax: +55 48 3331 9672. E-mail address: analucia@mbox1.ufsc.br (A.L.S. Rodrigues). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.05.016