RATIONALE: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. OBJECTIVE: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. METHODS: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents. RESULTS: 7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither L-arginine, nor D-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. L-Arginine but not D-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. CONCLUSIONS: Our findings suggest that NO might be an important modulator of depression in rats.
RATIONALE: There is some strong evidence about the role of nitric oxide (NO) as an intercellular messenger in central physiological mechanisms. NO is synthesized from L-arginine by nitric oxide synthase (NOS), as a response to activation of N-methyl-D-aspartate (NMDA) receptors by excitatory amino acids. NMDA receptor antagonists also produce antidepressant-like actions in preclinical models. OBJECTIVE: In the present study, the involvement of NO in the mechanism of depression was investigated. 7-Nitroindazole (7-NI) (15, 30, 60, 90 mg/kg IP), a selective inhibitor of neuronal NOS was examined. METHODS: The Porsolt forced swimming test (FST) has been used as a test for screening new antidepressant agents. RESULTS:7-NI dose-dependently decreased the immobility time in FST, but produced no significant change in locomotor activity in naive rats. Neither L-arginine, nor D-arginine (100 mg/kg) affected the immobility time in the FST or revealed any effect on locomotion. L-Arginine but not D-arginine, given 10 min before 7-NI, reversed the 7-NI-induced effect on immobility time. CONCLUSIONS: Our findings suggest that NO might be an important modulator of depression in rats.
Authors: Samer Abdul-Hay; Isaac T Schiefer; R Esala P Chandrasena; Min Li; Ramy Abdelhamid; Yue-Ting Wang; Ehsan Tavassoli; Bradley Michalsen; Rezene T Asghodom; Jia Luo; Gregory R J Thatcher Journal: ACS Med Chem Lett Date: 2011-09-08 Impact factor: 4.345
Authors: Michelle Silva; Daniele C Aguiar; Cassiano R A Diniz; Francisco Silveira Guimarães; Sâmia R L Joca Journal: Cell Mol Neurobiol Date: 2011-11-27 Impact factor: 5.046
Authors: Vishal Bali; Michael L Johnson; Hua Chen; Marc L Fleming; Holly M Holmes; Rajender R Aparasu Journal: Ann Pharmacother Date: 2015-11-25 Impact factor: 3.154