Copland A M, Balfour D J
Department of Pharmacology and Clinical Pharmacology University of Dundee, Ninewells Hospital and Medical School, Scotland.
Pharmacol Biochem Behav. 1987 Aug;27(4):619-24. doi: 10.1016/0091-3057(87)90183-3.
Diazepam, administered to rats at a high dose (25 mg/kg PO) has been shown to have no effect on the plasma corticosterone response to the stress of an elevated open platform. It did however, reduce the plasma corticosterone in rats repeatedly exposed to the apparatus. Diazepam-withdrawal from stress-habituated rats increased plasma corticosterone (p less than 0.01) whereas withdrawal of diazepam from unstressed rats had no effect on plasma corticosterone. It is concluded that this effect of diazepam-withdrawal may reflect the development of dependence upon the drug. Significant effects were not observed following the administration of a lower non-selective dose (5 mg/kg PO) of diazepam and, therefore, it is not clear whether dependence to its sedative, rather than the anxiolytic properties have been measured. Acute diazepam (25 mg/kg) increased (p less than 0.05) hippocampal 5-hydroxyindoleacetic acid; its withdrawal from unstressed rats after 40 days reduced (p less than 0.01) hypothalamic 5-hydroxytryptamine. There was no evidence that the effects of diazepam or its withdrawal on plasma corticosterone in stressed rats were associated directly with changes in brain 5-hydroxyindoles.
已证明，以高剂量（25毫克/千克，口服）给大鼠施用安定，对其血浆皮质酮对应激性高架开放平台的反应没有影响。然而，它确实降低了反复接触该装置的大鼠的血浆皮质酮水平。从应激习惯化大鼠中撤掉安定会增加血浆皮质酮（p<0.01），而从未受应激的大鼠中撤掉安定对血浆皮质酮没有影响。得出的结论是，撤掉安定的这种效应可能反映了对该药物依赖性的发展。施用较低的非选择性剂量（5毫克/千克，口服）的安定后未观察到显著效应，因此，尚不清楚所测定的是否是对其镇静作用而非抗焦虑特性的依赖性。急性给予安定（25毫克/千克）会增加（p<0.05）海马5-羟吲哚乙酸；在40天后从未受应激的大鼠中撤掉安定会降低（p<0.01）下丘脑5-羟色胺。没有证据表明安定或其撤药对应激大鼠血浆皮质酮的影响与脑5-羟吲哚的变化直接相关。
