Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, Haryana, India.
Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, Haryana, India.
Pharmacol Biochem Behav. 2018 Oct;173:96-106. doi: 10.1016/j.pbb.2018.06.001. Epub 2018 Jul 21.
Present study was carried out to investigate the 'anxiolytic-like' effect of pyridoxine in mice. Pyridoxine (90, 180 and 360 mg/kg) was administered by intraperitoneal (i.p.) route to the experimental mice and anxiety-related behavior was evaluated by light and dark box (LDB) and elevated plus maze (EPM) models. Glutamate, GABA and nitrite levels were also determined in the isolated whole brain of mice. It was observed that pyridoxine (180 mg/kg, i.p.) exerted 'anxiolytic-like' effect in mice in EPM and LDB models. Also, there was a significant increase in the levels of GABA whereas; the levels of glutamate and nitrite were decreased as compared to the control group. Administration of pentamethylene tetrazole (PTZ; 20 mg/kg, i.p.) exerted anxiogenic effects in mice, but the combination of PTZ and pyridoxine (180 mg/kg, i.p.) abolished the 'anxiolytic-like' effect of pyridoxine, thereby, suggesting the possible role of GABA in the 'anxiolytic-like' effect of pyridoxine in mice. Further, the influence of NO-sGC-cGMP pathway was investigated by administering the sub-effective dose of pyridoxine in combination with sub-threshold doses of NO modulators i.e. l‑arginine (50 mg/kg, i.p.; NO donor); methylene blue (1 mg/kg, i.p.; NO and soluble guanylate cyclase inhibitor) and sildenafil (1 mg/kg, i.p.; phosphodiesterase inhibitor and cGMP modulator). It was observed that the 'anxiolytic-like' effect of pyridoxine in mice was counteracted by the NO donor and potentiated by the NO inhibitors. Thus, the present study confirmed the involvement of GABAergic and NO-sGC-cGMP pathway in the 'anxiolytic-like' effect of pyridoxine in mice.
本研究旨在探讨吡哆醇在小鼠体内的“抗焦虑样”作用。吡哆醇（90、180 和 360mg/kg）通过腹腔内（i.p.）途径给予实验小鼠，并通过明暗箱（LDB）和高架十字迷宫（EPM）模型评估焦虑相关行为。还测定了小鼠分离全脑中的谷氨酸、GABA 和亚硝酸盐水平。结果表明，吡哆醇（180mg/kg，i.p.）在 EPM 和 LDB 模型中对小鼠表现出“抗焦虑样”作用。此外，与对照组相比，GABA 水平显著升高，而谷氨酸和亚硝酸盐水平降低。戊四氮（PTZ；20mg/kg，i.p.）给药在小鼠中产生焦虑作用，但 PTZ 和吡哆醇（180mg/kg，i.p.）的联合给药消除了吡哆醇的“抗焦虑样”作用，从而表明 GABA 在吡哆醇的“抗焦虑样”作用中可能发挥作用在小鼠中。此外，通过给予亚有效剂量的吡哆醇与亚阈值剂量的 NO 调节剂（即 l-精氨酸（50mg/kg，i.p.；NO 供体）；亚甲蓝（1mg/kg，i.p.；NO 和可溶性鸟苷酸环化酶抑制剂）和西地那非（1mg/kg，i.p.；磷酸二酯酶抑制剂和 cGMP 调节剂）联合给药，研究了 NO-sGC-cGMP 途径的影响。结果表明，吡哆醇在小鼠中的“抗焦虑样”作用被 NO 供体抵消，被 NO 抑制剂增强。因此，本研究证实了 GABA 能和 NO-sGC-cGMP 途径参与了吡哆醇在小鼠中的“抗焦虑样”作用。
