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Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test.
Eur Neuropsychopharmacol 2010; 20(11):793-801EN

Abstract

Escitalopram is a serotonin reuptake inhibitor used in the treatment of depression and anxiety disorders. This study investigated the effect of escitalopram in forced swimming test (FST) and in the tail suspension test (TST) in mice, and tested the hypothesis that the inhibition of NMDA receptors and NO-cGMP synthesis is implicated in its mechanism of action in the FST. Escitalopram administered by i.p. route reduced the immobility time both in the FST (0.3-10 mg/kg) and in the TST (0.1-10 mg/kg). Administration of escitalopram by p.o route (0.3-10 mg/kg) also reduced the immobility time in the FST. The antidepressant-like effect of escitalopram (3mg/kg, p.o.) in the FST was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (50 mg/kg, i.p., a neuronal nitric oxide synthase inhibitor), methylene blue (20 mg/kg, i.p., an inhibitor of both nitric oxide synthase and soluble guanylate cyclase) or ODQ (30 pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a subeffective dose of escitalopram (0.1 mg/kg, p.o.) reduced the immobility time in the FST as compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the open-field test. Altogether, our data suggest that the antidepressant-like effect of escitalopram is dependent on inhibition of either NMDA receptors or NO-cGMP synthesis. The results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of escitalopram and reinforce the role of NMDA receptors and l-arginine-NO-GMP pathway in the mechanism of action of antidepressant agents.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

20810255

Citation

Zomkowski, Andréa D E., et al. "Involvement of NMDA Receptors and L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway in the Antidepressant-like Effects of Escitalopram in the Forced Swimming Test." European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, vol. 20, no. 11, 2010, pp. 793-801.
Zomkowski AD, Engel D, Gabilan NH, et al. Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. Eur Neuropsychopharmacol. 2010;20(11):793-801.
Zomkowski, A. D., Engel, D., Gabilan, N. H., & Rodrigues, A. L. (2010). Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology, 20(11), pp. 793-801. doi:10.1016/j.euroneuro.2010.07.011.
Zomkowski AD, et al. Involvement of NMDA Receptors and L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway in the Antidepressant-like Effects of Escitalopram in the Forced Swimming Test. Eur Neuropsychopharmacol. 2010;20(11):793-801. PubMed PMID: 20810255.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. AU - Zomkowski,Andréa D E, AU - Engel,Daiane, AU - Gabilan,Nelson H, AU - Rodrigues,Ana Lúcia S, PY - 2010/04/01/received PY - 2010/06/09/revised PY - 2010/07/23/accepted PY - 2010/9/3/entrez PY - 2010/9/3/pubmed PY - 2011/8/25/medline SP - 793 EP - 801 JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JO - Eur Neuropsychopharmacol VL - 20 IS - 11 N2 - Escitalopram is a serotonin reuptake inhibitor used in the treatment of depression and anxiety disorders. This study investigated the effect of escitalopram in forced swimming test (FST) and in the tail suspension test (TST) in mice, and tested the hypothesis that the inhibition of NMDA receptors and NO-cGMP synthesis is implicated in its mechanism of action in the FST. Escitalopram administered by i.p. route reduced the immobility time both in the FST (0.3-10 mg/kg) and in the TST (0.1-10 mg/kg). Administration of escitalopram by p.o route (0.3-10 mg/kg) also reduced the immobility time in the FST. The antidepressant-like effect of escitalopram (3mg/kg, p.o.) in the FST was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (50 mg/kg, i.p., a neuronal nitric oxide synthase inhibitor), methylene blue (20 mg/kg, i.p., an inhibitor of both nitric oxide synthase and soluble guanylate cyclase) or ODQ (30 pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a subeffective dose of escitalopram (0.1 mg/kg, p.o.) reduced the immobility time in the FST as compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the open-field test. Altogether, our data suggest that the antidepressant-like effect of escitalopram is dependent on inhibition of either NMDA receptors or NO-cGMP synthesis. The results contribute to the understanding of the mechanisms underlying the antidepressant-like effect of escitalopram and reinforce the role of NMDA receptors and l-arginine-NO-GMP pathway in the mechanism of action of antidepressant agents. SN - 1873-7862 UR - https://www.unboundmedicine.com/medline/citation/20810255/Involvement_of_NMDA_receptors_and_L_arginine_nitric_oxide_cyclic_guanosine_monophosphate_pathway_in_the_antidepressant_like_effects_of_escitalopram_in_the_forced_swimming_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-977X(10)00168-9 DB - PRIME DP - Unbound Medicine ER -