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在正常或利血平化小鼠中使用悬尾试验检测不同抗抑郁药物的抗不动活性。

Anti-immobility activity of different antidepressant drugs using the tail suspension test in normal or reserpinized mice.

作者信息

Teste J F, Pelsy-Johann I, Decelle T, Boulu R G

机构信息

Département Recherche, Coopération Pharmaceutique Française, La Rochette, France.

出版信息

Fundam Clin Pharmacol. 1993;7(5):219-26. doi: 10.1111/j.1472-8206.1993.tb00235.x.

Abstract

The tail suspension test is a screening procedure recently used in mice to detect antidepressant activity of drugs. The ability of amine re-uptake inhibitors to decrease immobility in non-reserpinized and in reserpinized mice was studied. Reserpine (4 mg/kg ip) was injected 4 h previously. Anti-depressants were administered ip, 60 min before tail suspension. Animal activity was recorded for 6 min. Preferential serotonin re-uptake blockers (fluoxetine, fluvoxamine, clomipramine) were poorly active in non-reserpinized mice and inactive in reserpine-treated mice. Noradrenergic drugs (desipramine, demexiptiline, viloxazine) were more efficient in reserpinized than in non-reserpinized mice. The mixed serotonin-noradrenaline re-uptake inhibitor (imipramine) shows an activity which should be considered between serotonin re-uptake inhibitors and noradrenaline re-uptake inhibitors. DA re-uptake inhibitors (amineptine, GBR 12909) exhibited the highest anti-immobility effect in non reserpinized animals but were of low efficacy after reserpine treatment. Amphetamine differed from dopamine re-uptake inhibitors by its better activity in reserpinized animals. Moreover, it was the only drug showing an equal anti-immobility effect in non reserpinized and reserpinized mice because the dose of 8 mg/kg of amphetamine reduced immobility in reserpinized mice with the same intensity as the dose of 4 mg/kg in non reserpinized mice whereas no other drugs tested in this study achieved the same effect. Comparison of anti-immobility activities of putative anti-depressants in non-pre-treated and in reserpine-pre-treated mice, using the tail suspension test, may be useful to discriminate amphetamines from antidepressant drugs and to differentiate between categories of amine re-uptake blockers.

摘要

尾悬挂试验是最近在小鼠中用于检测药物抗抑郁活性的一种筛选程序。研究了胺再摄取抑制剂在未用利血平处理和用利血平处理的小鼠中降低不动时间的能力。利血平(4mg/kg,腹腔注射)在4小时前注射。抗抑郁药在尾悬挂前60分钟腹腔注射。记录动物6分钟的活动情况。选择性5-羟色胺再摄取阻滞剂(氟西汀、氟伏沙明、氯米帕明)在未用利血平处理的小鼠中活性较差,在利血平处理的小鼠中无活性。去甲肾上腺素能药物(地昔帕明、地美替林、维洛沙嗪)在利血平处理的小鼠中比在未用利血平处理的小鼠中更有效。5-羟色胺-去甲肾上腺素再摄取混合抑制剂(丙咪嗪)表现出的活性介于5-羟色胺再摄取抑制剂和去甲肾上腺素再摄取抑制剂之间。多巴胺再摄取抑制剂(阿密曲替林、GBR 12909)在未用利血平处理的动物中表现出最高的抗不动作用,但在利血平处理后效果不佳。苯丙胺与多巴胺再摄取抑制剂不同,它在利血平处理的动物中活性更好。此外,它是唯一一种在未用利血平处理和用利血平处理的小鼠中表现出相同抗不动作用的药物,因为8mg/kg剂量的苯丙胺降低利血平处理小鼠的不动时间的强度与4mg/kg剂量降低未用利血平处理小鼠的不动时间的强度相同,而本研究中测试的其他药物均未达到相同效果。使用尾悬挂试验比较假定抗抑郁药在未预处理和利血平预处理小鼠中的抗不动活性,可能有助于区分苯丙胺类药物和抗抑郁药,并区分胺再摄取阻滞剂的类别。

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