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Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12; 32(8):1838-43.PN

Abstract

Tramadol is a centrally acting analgesic which is used mainly for the treatment of moderate or severe pain. It is a synthetic opioid in the aminocyclohexanol group that binds weakly to micro-opioid receptors. Since it has been suggested that both opioid and monoaminergic systems play a role in depressive disorders, tramadol has been studied in the forced swimming test (FST). The present study was designed to explore the antidepressant activity of tramadol in rat FST and its possible mechanisms of action. The involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant action of tramadol was investigated. Treatment with tramadol, given (30 min earlier) by oral route (p.o.) at the doses of 10, 20 and 40 mg/kg, decreased immobility time in the FST. Pretreatment of rats with L-arginine (250 mg/kg, intraperitoneal, i.p., a nitric oxide precursor) or sildenafil (5 mg/kg, i.p., a phosphodiesterase 5 inhibitor, PDE5) significantly reversed the reduction in immobility time elicited by tramadol (20 mg/kg, p.o.) in the FST. Treatment of animals with a sub-effective dose of tramadol (5 mg/kg, p.o.) produced a synergistic antidepressant-like effect with N(G)-nitro-L-arginine (L-NNA, 3 mg/kg, i.p., an inhibitor of nitric oxide synthase) or with 7-nitroindazole (7-NI, 9 mg/kg i.p., a specific neuronal nitric oxide synthase inhibitor) in the FST. Pretreatment of animals with methylene blue (3.75 mg/kg i.p., an inhibitor of NO synthase and soluble guanylate cyclase - sGC) or (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (ODQ, 2 mg/kg, i.p., a specific inhibitor of sGC) significantly caused a synergistic effect with a sub-effective dose of tramadol (5 mg/kg, p.o.) in the FST. In the present study, different doses of tramadol and the combination with the L-arginine-NO-cGMP pathway modulators had no effect on the locomotor activity of rats in the open-field test. Thus, our findings suggest that the acute administration of tramadol produces antidepressant-like effect in the rat FST by a mechanism that involves the inhibition of L-arginine-NO-cGMP pathway.

Authors+Show Affiliations

Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria (UFSM), Santa Maria, CEP 97105-900, RS, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18773934

Citation

Jesse, Cristiano R., et al. "Involvement of L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway in the Antidepressant-like Effect of Tramadol in the Rat Forced Swimming Test." Progress in Neuro-psychopharmacology & Biological Psychiatry, vol. 32, no. 8, 2008, pp. 1838-43.
Jesse CR, Bortolatto CF, Savegnago L, et al. Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(8):1838-43.
Jesse, C. R., Bortolatto, C. F., Savegnago, L., Rocha, J. B., & Nogueira, C. W. (2008). Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. Progress in Neuro-psychopharmacology & Biological Psychiatry, 32(8), 1838-43. https://doi.org/10.1016/j.pnpbp.2008.08.010
Jesse CR, et al. Involvement of L-arginine-nitric Oxide-cyclic Guanosine Monophosphate Pathway in the Antidepressant-like Effect of Tramadol in the Rat Forced Swimming Test. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1838-43. PubMed PMID: 18773934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tramadol in the rat forced swimming test. AU - Jesse,Cristiano R, AU - Bortolatto,Cristiani F, AU - Savegnago,Lucielli, AU - Rocha,João B T, AU - Nogueira,Cristina W, Y1 - 2008/08/23/ PY - 2008/05/20/received PY - 2008/07/29/revised PY - 2008/08/13/accepted PY - 2008/9/9/pubmed PY - 2009/4/16/medline PY - 2008/9/9/entrez SP - 1838 EP - 43 JF - Progress in neuro-psychopharmacology & biological psychiatry JO - Prog. Neuropsychopharmacol. Biol. Psychiatry VL - 32 IS - 8 N2 - Tramadol is a centrally acting analgesic which is used mainly for the treatment of moderate or severe pain. It is a synthetic opioid in the aminocyclohexanol group that binds weakly to micro-opioid receptors. Since it has been suggested that both opioid and monoaminergic systems play a role in depressive disorders, tramadol has been studied in the forced swimming test (FST). The present study was designed to explore the antidepressant activity of tramadol in rat FST and its possible mechanisms of action. The involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant action of tramadol was investigated. Treatment with tramadol, given (30 min earlier) by oral route (p.o.) at the doses of 10, 20 and 40 mg/kg, decreased immobility time in the FST. Pretreatment of rats with L-arginine (250 mg/kg, intraperitoneal, i.p., a nitric oxide precursor) or sildenafil (5 mg/kg, i.p., a phosphodiesterase 5 inhibitor, PDE5) significantly reversed the reduction in immobility time elicited by tramadol (20 mg/kg, p.o.) in the FST. Treatment of animals with a sub-effective dose of tramadol (5 mg/kg, p.o.) produced a synergistic antidepressant-like effect with N(G)-nitro-L-arginine (L-NNA, 3 mg/kg, i.p., an inhibitor of nitric oxide synthase) or with 7-nitroindazole (7-NI, 9 mg/kg i.p., a specific neuronal nitric oxide synthase inhibitor) in the FST. Pretreatment of animals with methylene blue (3.75 mg/kg i.p., an inhibitor of NO synthase and soluble guanylate cyclase - sGC) or (1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one) (ODQ, 2 mg/kg, i.p., a specific inhibitor of sGC) significantly caused a synergistic effect with a sub-effective dose of tramadol (5 mg/kg, p.o.) in the FST. In the present study, different doses of tramadol and the combination with the L-arginine-NO-cGMP pathway modulators had no effect on the locomotor activity of rats in the open-field test. Thus, our findings suggest that the acute administration of tramadol produces antidepressant-like effect in the rat FST by a mechanism that involves the inhibition of L-arginine-NO-cGMP pathway. SN - 0278-5846 UR - https://www.unboundmedicine.com/medline/citation/18773934/Involvement_of_L_arginine_nitric_oxide_cyclic_guanosine_monophosphate_pathway_in_the_antidepressant_like_effect_of_tramadol_in_the_rat_forced_swimming_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-5846(08)00247-9 DB - PRIME DP - Unbound Medicine ER -