mCPP-induced anxiety in the light-dark box in rats -: a new method for screening anxiolytic activity

mCPP-induced anxiety in the light-dark box in rats -: a new method for screening anxiolytic activity
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DOI:
10.1007/s002130050568
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发表时间:
1998-04-01
期刊:
影响因子:
3.4
通讯作者:
Lévay, G
Lévay, G
中科院分区:
医学3区
文献类型:
--
作者:
Bilkei-Gorzó, A;Gyertyán, I;Lévay, G

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抗焦虑药和其他药物的活性在光暗试验的情况下进行了研究,在大鼠与抗焦虑化合物III-氯苯基-哌嗪(mCPP)。mCPP 0.5 mg/kg显著降低了动物在装置光室中的探索活动。当单独研究时(不与mCPP组合),待测试的药物对mCPP诱导的焦虑没有显著改变大鼠在明暗装置中的活动,但育亨宾除外,其减少了照亮区域的运动时间值。1,4-苯二氮卓类药物[地西泮(0.1-4 mg/kg)和利血平(2- 8 mg/kg)]、5-HT_(2A/2C)拮抗剂[利坦色林(0.25-8 mg/kg)和德伦环烷(0.5-8 g/kg)]、5-HT_3拮抗剂MDL-72222(3 mg/kg)和乙醇(2-4 mg/kg)可显著降低mCPP的作用。在2,3-苯二氮卓类girisopam(2.5-5 mg/kg)给药组中发现mCPP给药动物的探索活性呈剂量依赖性增加。另一种2,3-苯二氮卓类分子托非索泮也显示出对mCPP的活性,尽管其作用不具有统计学显著性。5-HT 1A部分激动剂丁螺环酮在0.25-0.5 mg/kg的剂量范围内也有活性,而5-HT 1A完全激动剂8-OH-DPAT是唯一一种推定具有抗焦虑活性的药物,在该模型中明显缺乏任何作用。丙咪嗪、阿米替林、吗啡、纳洛酮、氟哌啶醇、氯氮平、苯丙胺、育亨宾、卡马西平和苯妥英钠无效。我们的结论是,mCPP诱导的焦虑在光-暗箱是一个有效的和有用的方法,用于筛选和检测抗焦虑活性的广泛的化合物与各种模式的行动。
The activity of anxiolytic and other drugs in a light-dark test situation was studied in rats treated with the anxiogenic compound III-chlorophenyl-piperazine (mCPP). mCPP 0.5 mg/kg significantly diminished the exploratory activity of the animals in the light compartment of the apparatus. Drugs to be tested against mCPP-induced anxiety when studied alone (not in combination with mCPP) did not significantly alter the activity of rats in the light-dark apparatus, except yohimbine, which reduced the movement time values in the lit area. 1,4-Benzodiazepines [diazepam (0.1-4 mg/kg) and chlordiazepoxide (2-8mg/kg)], 5-HT2A/2C antagonists [ritanserin (0.25-8 mg/kg) and deramciclane (0.5-8 g/k,)], the 5-HT3 antagonist MDL-72222 (3mg/kg) and ethanol (2-4 mg/kg) significantly reduced the effect of mCPP. A dose-dependent increase in the exploratory activity of mCPP-treated animals was found in the 2,3-benzodiazepine girisopam (2.5-5 mg/kg)-treated groups. Tofisopam, another 2,3-benzodiazepine molecule, also showed activity against mCPP, although its effect was not statistically significant. The 5-HT1A partial agonist buspirone was also active in the dose range of 0.25-0.5 mg/kg, while the 5-HT1A full agonist 8-OH-DPAT was the only drug with presumed anxiolytic activity that clearly lacked any effect in this model. Imipramine, amitriptyline, morphine, naloxone, haloperidol, clozapine, amphetamine, yohimbine, carbamazepine and diphenylhydantoin were not effective. We conclude that mCPP-induced anxiety in the light-dark box is a potent and useful method for screening and detecting anxiolytic activity of a wide range of compounds with various modes of action.