Bourin M
Department of Pharmacology, Faculty of Medicine, Nantes, France.
Fundam Clin Pharmacol. 1990;4(1):49-64. doi: 10.1111/j.1472-8206.1990.tb01016.x.
Behavioural tests for predicting antidepressant activity in the animal provide a closer approximation than other tests of states of depression in man but are often long and costly to perform (except the behavioural despair test). The tests proposed here presuppose a pharmacological interaction (except the Porsolt test) but are simple enough to allow screening: included are antagonism of reserpine hypothermia, ptosis and akinesia; antagonism of effects induced by oxotremorine; antagonism of high-dose apomorphine; and potentiation of yohimbine toxicity. In combination with the study of motor activity in the mouse, these tests allow assessment of the specificity of antidepressant activity by establishing a ratio between the "antidepressant" dose and the "stimulant" or "sedative" dose. It can be predicted that a substance will be antidepressant and sedative or stimulant at the same dose if the ratio is close to 1; if the ratio is less than 1, at antidepressant doses the substance will be very sedative or stimulant according to the case. The specificity of the tests discussed can be debatable. Antagonism of reserpine-induced hypothermia indicates substances with direct or indirect beta-mimetic activity, ptosis antagonism, substances with alpha-adrenergic (not antidepressants) or serotoninergic (possibly antidepressants) activity; and akinesia antagonism, a direct or indirect dopaminergic activity (sometimes found in antidepressants) with psychostimulant activity. The oxotremorine test is related to the anticholinergic activity of substances, except in the case of hypothermia antagonism. The high-dose apomorphine test seems to be specific for substances inhibiting norepinephrine reuptake. The yohimbine test is simple to carry out, relatively inexpensive and does not fail to screen any molecule known to be effective to-date. The behavioural despair test is a good complement for screening except for drugs having a beta-agonist activity, it appears that this test is dependent on functional relationships between alpha 2 and serotonergic systems.
用于预测动物抗抑郁活性的行为测试比其他人类抑郁状态测试更接近实际情况，但通常实施起来耗时且成本高（行为绝望测试除外）。这里提出的测试预先假定存在药理相互作用（波索尔特测试除外），但足够简单以便进行筛选：包括利血平低温、眼睑下垂和运动不能的拮抗作用；毒蕈碱震颤素诱导效应的拮抗作用；高剂量阿扑吗啡的拮抗作用；以及育亨宾毒性的增强作用。结合对小鼠运动活性的研究，这些测试通过建立“抗抑郁”剂量与“兴奋”或“镇静”剂量之间的比率来评估抗抑郁活性的特异性。可以预测，如果该比率接近1，则一种物质在相同剂量下将具有抗抑郁和镇静或兴奋作用；如果该比率小于1，在抗抑郁剂量下该物质将根据具体情况非常镇静或兴奋。所讨论测试的特异性可能存在争议。利血平诱导的低温拮抗作用表明具有直接或间接β-拟交感活性的物质，眼睑下垂拮抗作用表明具有α-肾上腺素能（非抗抑郁药）或5-羟色胺能（可能是抗抑郁药）活性的物质；运动不能拮抗作用表明具有直接或间接多巴胺能活性（有时在抗抑郁药中发现）且具有精神兴奋活性的物质。毒蕈碱震颤素测试与物质的抗胆碱能活性有关，但低温拮抗作用的情况除外。高剂量阿扑吗啡测试似乎对抑制去甲肾上腺素再摄取的物质具有特异性。育亨宾测试实施简单、成本相对较低，并且不会漏筛任何迄今已知有效的分子。行为绝望测试是筛选的良好补充，除了具有β-激动剂活性的药物外，该测试似乎依赖于α2和5-羟色胺能系统之间的功能关系。
