Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats
Tipepidine, a non-narcotic antitussive, exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone-treated rats
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DOI：
10.1016/j.bbr.2015.12.008
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发表时间：
2016-04-01
影响因子：
2.7
通讯作者：
Takahama, Kazuo
中科院分区：
文献类型：
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作者：
Kawaura, Kazuaki;Ogata, Yukino;Takahama, Kazuo
我们研究了在促肾上腺皮质激素（ACTH）治疗的大鼠，这是一种治疗抵抗性抑郁症模型的强迫游泳试验中，替匹定是否发挥抗抑郁样作用，我们研究了替匹定的药理学机制的影响。本研究中使用雄性Wistar大鼠（5-7周龄）。替匹定（20和40 mg/kg，i. p.）减少ACTH处理大鼠在强迫游泳试验中的不动时间。替匹定的抗不动作用被儿茶酚胺消耗剂α-甲基-p-酪氨酸（300 mg/kg，s.c.）阻断，但不是由一种能减少维生素E的物质对氯苯丙氨酸引起的。多巴胺D-1受体拮抗剂SCH 23390（0.02 mg/kg，s.c.）和肾上腺素α（2）受体拮抗剂育亨宾（2 mg/kg，腹膜内）。在微透析技术中，替匹定（40 mg/kg，i. p.）增加ACTH处理的大鼠中脑外侧核（NAc）的细胞外多巴胺水平。(C)2016由Elsevier B. V.出版
We investigated whether tipepidine exerts an antidepressant-like effect in the forced swimming test in adrenocorticotropic hormone (ACTH)-treated rats, which is known as a treatment-resistant depression model, and we studied the pharmacological mechanisms of the effects of tipepidine. Male Wistar rats (5-7 weeks old) were used in this study. Tipepidine (20 and 40 mg/kg, i.p.) decreased the immobility time in the forced swimming test in ACTH-treated rats. The anti-immobility effect of tipepidine was blocked by a catecholamine-depleting agent, alpha-methyl-p-tyrosine (300 mg/kg, s.c.), but not by a serotonin-depleting agent, p-chlorophenylalanine. The anti-immobility effect of tipepidine was also blocked by a dopamine D-1 receptor antagonist, SCH23390 (0.02 mg/kg, s.c.) and an adrenaline alpha(2) receptor antagonist, yohimbine (2 mg/kg, i.p.). In microdialysis technique, tipepidine (40 mg/kg, i.p.) increased the extracellular dopamine level of the nucleus accumbens (NAc) in ACTH-treated rats. (C) 2016 Published by Elsevier B.V.