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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The pituitary-adrenal axis and the different behavioral effects of buspirone and chlordiazepoxide.
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The pituitary-adrenal axis and the different behavioral effects of buspirone and chlordiazepoxide.

机译：垂体-肾上腺轴和丁螺环酮和氯二氮卓的不同行为作用。

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Benzodiazepines and the novel anxiolytic buspirone share a common capacity to relieve clinical anxiety but do not share any side effects. Anxiety releases stress hormones and, at moderate doses, anxiolytic benzodiazepines block this release. It is interesting, therefore, that buspirone and other 5-HT1A agonists release stress hormones at moderate doses. Both the U-shaped dose-response curve seen with buspirone in some animal tests of anxiety and its slow onset of clinical action could be attributed to this release of stress hormones. Metyrapone (200 mg/kg), an inhibitor of 11-beta-hydroxylase, was used in the present experiments as a form of chemical adrenalectomy and was combined with administration of corticosterone (1 mg) to produce rats with presumed approximately normal corticosterone levels but no capacity to release endogenous corticosterone. This treatment reduced the difference normally observed in the effects of chlordiazepoxide (5 mg/kg) and buspirone (0.37 mg/kg) on a fixed interval schedule particularly in the early part of the interval when release of behavioral inhibition would be expected to contribute most to the effects. These results are consistent with the previous suggestion of Johnston and File (8) that the anxiolytic action of buspirone may be counteracted by activation of the pituitary-adrenal axis. Corticosterone appears to be the most likely critical agent for this antagonist action in the present experiments, although CRF and ACTH are also possibilities. It is likely that there is a mutual functional opposition between endogenous anxiolytic factors and stress hormones.
机译：苯二氮卓类药物和新型抗焦虑药丁螺环酮具有缓解临床焦虑症的共同能力，但没有任何副作用。焦虑会释放压力激素，在中等剂量时，抗焦虑的苯二氮卓类药物会阻止这种释放。因此，有趣的是，丁螺环酮和其他5-HT1A激动剂以中等剂量释放应激激素。在一些动物实验性焦虑试验中，丁螺环酮所见的U形剂量反应曲线及其临床动作起效缓慢都可能归因于这种压力激素的释放。 Metyrapone（200 mg / kg）是11-β-羟化酶的抑制剂，在本实验中以化学性肾上腺切除术的形式使用，并与皮质酮（1 mg）联合给药以产生假定皮质酮水平大致正常的大鼠，但没有释放内源性皮质酮的能力。这种治疗减少了在固定的时间间隔计划中通常观察到的氯二氮卓（5 mg / kg）和丁螺环酮（0.37 mg / kg）的作用之间的差异，特别是在该时间间隔的早期阶段，预计行为抑制的释放将起最大作用效果。这些结果与Johnston和File（8）先前的建议一致，即丁螺环酮的抗焦虑作用可能通过垂体-肾上腺轴的激活而抵消。尽管CRF和ACTH也是可能的，但是皮质酮似乎是本实验中该拮抗剂作用的最可能的关键药物。内源性抗焦虑因子和应激激素之间可能存在相互的功能对立。

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