Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, 88040-900, SC, Brazil.
Behav Brain Res. 2011 Nov 20;225(1):328-33. doi: 10.1016/j.bbr.2011.07.024. Epub 2011 Jul 23.
Clinical and preclinical data reported that ascorbic acid has antidepressant properties. The present study was designed to investigate the participation of l-arginine-NO-cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test (TST) in mice. The antidepressant-like effect of ascorbic acid (1mg/kg, p.o.) in the TST was prevented by the pre-treatment of mice with NMDA (0.1pmol/site, i.c.v.), l-arginine (750mg/kg, i.p., a substrate for nitric oxide synthase) or sildenafil (5mg/kg, i.p., a phosphodiesterase 5 inhibitor). The administration of MK-801 (0.001mg/kg, i.p), 7-nitroindazole (25mg/kg, i.p., a neuronal nitric oxide synthase inhibitor) or ODQ (30pmol/site i.c.v., a soluble guanylate cyclase inhibitor) in combination with a sub-effective dose of ascorbic acid (0.1mg/kg, p.o.) reduced the immobility time in the TST test when compared with either drug alone. None of the results in the TST appears to be due to a nonspecific locomotor effect. Our findings provide evidence that the effect of ascorbic acid in the TST involve an interaction with NMDA receptors and l-arginine-NO-cGMP pathway, contributing to the understanding of the mechanisms underlying the antidepressant-like effect of this vitamin.
临床前和临床数据表明抗坏血酸具有抗抑郁作用。本研究旨在探讨 l-精氨酸-NO-cGMP 途径在抗坏血酸抗抑郁样作用中的参与情况，该作用是通过在小鼠悬尾试验（TST）中观察得到的。抗坏血酸（1mg/kg，p.o.）在 TST 中的抗抑郁样作用被 NMDA（0.1pmol/site，i.c.v.）、l-精氨酸（750mg/kg，i.p.，一氧化氮合酶的底物）或西地那非（5mg/kg，i.p.，磷酸二酯酶 5 抑制剂）预处理所阻止。MK-801（0.001mg/kg，i.p.）、7-硝基吲唑（25mg/kg，i.p.，神经元型一氧化氮合酶抑制剂）或 ODQ（30pmol/site，i.c.v.，可溶性鸟苷酸环化酶抑制剂）与亚有效剂量抗坏血酸（0.1mg/kg，p.o.）联合给药可降低 TST 试验中的不动时间，与单独使用任何一种药物相比均有此效果。TST 中的结果似乎都不是由于非特异性运动效应引起的。我们的研究结果提供了证据，表明抗坏血酸在 TST 中的作用涉及与 NMDA 受体和 l-精氨酸-NO-cGMP 途径的相互作用，有助于理解这种维生素的抗抑郁样作用的机制。
