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Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways.
Behav Brain Res 2012; 234(2):137-48BB

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.

Authors+Show Affiliations

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, 88040-900, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22743004

Citation

Bettio, Luis E B., et al. "Guanosine Produces an Antidepressant-like Effect Through the Modulation of NMDA Receptors, Nitric oxide-cGMP and PI3K/mTOR Pathways." Behavioural Brain Research, vol. 234, no. 2, 2012, pp. 137-48.
Bettio LE, Cunha MP, Budni J, et al. Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways. Behav Brain Res. 2012;234(2):137-48.
Bettio, L. E., Cunha, M. P., Budni, J., Pazini, F. L., Oliveira, Á., Colla, A. R., & Rodrigues, A. L. (2012). Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways. Behavioural Brain Research, 234(2), pp. 137-48. doi:10.1016/j.bbr.2012.06.021.
Bettio LE, et al. Guanosine Produces an Antidepressant-like Effect Through the Modulation of NMDA Receptors, Nitric oxide-cGMP and PI3K/mTOR Pathways. Behav Brain Res. 2012 Oct 1;234(2):137-48. PubMed PMID: 22743004.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Guanosine produces an antidepressant-like effect through the modulation of NMDA receptors, nitric oxide-cGMP and PI3K/mTOR pathways. AU - Bettio,Luis E B, AU - Cunha,Mauricio P, AU - Budni,Josiane, AU - Pazini,Francis L, AU - Oliveira,Ágatha, AU - Colla,André R, AU - Rodrigues,Ana Lúcia S, Y1 - 2012/06/26/ PY - 2012/02/07/received PY - 2012/06/13/revised PY - 2012/06/17/accepted PY - 2012/6/30/entrez PY - 2012/6/30/pubmed PY - 2013/1/23/medline SP - 137 EP - 48 JF - Behavioural brain research JO - Behav. Brain Res. VL - 234 IS - 2 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/22743004/Guanosine_produces_an_antidepressant_like_effect_through_the_modulation_of_NMDA_receptors_nitric_oxide_cGMP_and_PI3K/mTOR_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(12)00434-2 DB - PRIME DP - Unbound Medicine ER -