title: Involvement of nitric oxide-cGMP pathway in the antidepressant-like effects of adenosine in the forced swimming test.
abstract: We have previously shown that an acute administration of adenosine produces an antidepressant-like effect in the forced swimming test (FST) and in the tail suspension test in mice. In this work we investigated the contribution of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway to adenosine's antidepressant-like effect in the FST since this signalling pathway is assumed to play an important role in depression. The effect of adenosine (10 mg/kg i.p.) was prevented by pre-treatment with L-arginine (750 mg/kg i.p.), S-nitroso-N-acetyl-penicillamine (SNAP, 25 microg/site i.c.v), or sildenafil (5 mg/kg i.p.), but not with D-arginine (750 mg/kg i.p.). Treatment of mice with N(G)-nitro-L-arginine ( L-NNA, 0.03 and 0.3 mg/kg i.p.), Methylene Blue (18 mg/kg i.p.), or ODQ (30 pmol/site i.c.v.) potentiated the effect of adenosine (1 mg/kg i.p.) in the FST. The reduction of immobility time elicited by adenosine (10 mg/kg i.p.) in the FST was prevented by pre-treatment with sildenafil (0.5 and 5 mg/kg i.p.). Together the results indicate that the effect of adenosine in the FST appears to be mediated through an interaction with the NO-cGMP pathway.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário Trindade - 88040-900, Florianópolis-SC, Brasil.
authors.forename: Manuella Pinto
authors.initials: MP
authors.lastname: Kaster
authors.forename: Angelo Oscar
authors.initials: AO
authors.lastname: Rosa
authors.forename: Adair R S
authors.initials: AR
authors.lastname: Santos
authors.forename: Ana Lúcia S
authors.initials: AL
authors.lastname: Rodrigues
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D001120:Arginine; D000068677:Sildenafil Citrate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D006152:Cyclic GMP; D000241:Adenosine