Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 234, Issue 2, Pages 137-148Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2012.06.021
Keywords
Antidepressant; Guanosine; Tail suspension test; Forced swimming test; NMDA; L-Arginine-nitric oxide
Categories
Funding
- IBN-Net/CNPq
- CNPq
- CAPES
- FAPESC
- NENASC project (PRONEX program CNPq/FAPESC)
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Guanosine is an extracellular signaling molecule implicated in the modulation of glutamatergic transmission and neuroprotection. The present study evaluated the antidepressant-like effect of guanosine in the forced swimming test (FST) and in the tail suspension test (TST) in mice. The contribution of NMDA receptors as well as L-arginine-NO-cGMP and PI3K-mTOR pathways to this effect was also investigated. Guanosine administered orally produced an antidepressant-like effect in the FST (0.5-5 mg/kg) and TST (0.05-0.5 mg/kg). The anti-immobility effect of guanosine in the TST was prevented by the treatment of mice with NMDA (0.1 pmol/site, icy.), D-serine (30 mu g/site, i.c.v., a co-agonist of NMDA receptors), L-arginine (750 mg/kg, i.p., a substrate for nitric oxide synthase), sildenafil (5 mg/kg, i.p., a phosphodiesterase 5 inhibitor), I.Y294002 (10 mu g/site, i.c.v., a reversible PI3K inhibitor), wortmannin (0.1 mu g/site, an irreversible PI3K inhibitor) or rapamycin (0.2 nmol/site, icy., a selective mTOR inhibitor). In addition, the administration of ketamine (0.1 mg/kg, i.p., a NMDA receptor antagonist), MK-801 (0.001 mg/kg, i.p., another NMDA receptor antagonist), 7-nitroindazole (50 mg/kg, i.p., a neuronal nitric oxide synthase inhibitor) or ODQ (30 pmol/site icy., a soluble guanylate cyclase inhibitor) in combination with a sub-effective dose of guanosine (0.01 mg/kg, p.o.) reduced the immobility time in the TST when compared with either drug alone. None of the treatments affected locomotor activity. Altogether, results firstly indicate that guanosine exerts an antidepressant-like effect that seems to be mediated through an interaction with NMDA receptors, L-arginine-NO-cGMP and PI3K-mTOR pathways. (C) 2012 Elsevier B.V. All rights reserved.
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