Article ID Journal Published Year Pages File Type
4312940 Behavioural Brain Research 2012 12 Pages PDF
Abstract

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, i.c.v.), d-serine (30 μg/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), LY294002 (10 μg/site, i.c.v., a reversible PI3K inhibitor), wortmannin (0.1 μg/site, i.c.v., an irreversible PI3K inhibitor) or rapamycin (0.2 nmol/site, i.c.v., 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 i.c.v., 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.

► Guanosine exerts an antidepressant-like effect in two predictive animal models. ► NMDA and d-serine reversed the antidepressant-like effect of guanosine. ► The NO–cGMP pathway is involved in the anti-immobility effect of guanosine. ► Antidepressant-like effect of guanosine is mediated by PI3K/mTOR pathway.

Related Topics
Life Sciences Neuroscience Behavioral Neuroscience
Authors
, , , , , , ,