Diazepam attenuation of restraint stress-induced corticosterone levels is enhanced by prior exposure to repeated restraint
Diazepam attenuation of restraint stress-induced corticosterone levels is enhanced by prior exposure to repeated restraint
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DOI：
10.1016/s0306-4530(97)00026-7
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发表时间：
1997-07-01
影响因子：
3.7
通讯作者：
Spencer, RL
中科院分区：
文献类型：
--
作者：
Kalman, BA;Kim, PJ;Spencer, RL
先前的研究表明，地西泮降低下丘脑-垂体-肾上腺轴（HPA）的活动在紧张的情况下，但矛盾的是，作为一个刺激剂的基础轴活动。此外，一些研究人员报告说，低剂量的地西泮在降低应激诱导的皮质酮（CORT）水平方面无效，但类似剂量通常会对恐惧和焦虑的行为措施产生抗焦虑作用。我们研究了地西泮对雄性Sprague-Dawley大鼠血浆CORT水平的影响。与大多数文献一致，在束缚前1 h IP给予地西泮（1.5、3.0或6.0 mg/kg）以剂量依赖性方式增加非应激基线血浆CORT水平。在第一次暴露于Ih限制应激过程中，注射地西泮的大鼠的CORT水平与对照组的应激水平没有差异，除了在60分钟的应激时间点接受6.0 mg/kg的受试者。然而，地西泮+束缚治疗5天后，所有三种剂量的地西泮均能够减弱应激诱导的CORT增加。使用3.0 mg/kg剂量作为探针，发现该效应不依赖于地西泮的重复给药，而是依赖于重复暴露于束缚。这些结果表明，反复约束产生的变化，神经敏感性苯二氮卓类药物。(C)1997 Elsevier Science Ltd.
Prior research has demonstrated that diazepam decreases hypothalamic-pituitary-adrenal colter (HPA) axis activity in stressful contexts but, paradoxically, acts as a stimulator of basal axis activity. Also, several investigators have reported that low doses of diazepam are not effective in reducing stress-induced corticosterone (CORT) levels, yet similar doses typically produce anxiolytic effects on behavioral measures of fear and anxiety. We have examined the effects of diazepam on plasma CORT levels in male Sprague-Dawley rats utilizing a repeated restraint paradigm. Consistent with most literature, diazepam administered IP (1.5, 3.0, or 6.0 mg/kg) 1 h prior to restraint increased non-stress, baseline plasma CORT levels in a dose-dependent fashion. During the first exposure to the Ih restraint-stress procedure, CORT levels of diazepam-injected rats did not differ from the stress levels of controls except at the 60-min stress time point in those subjects receiving 6.0 mg/kg. However, diazepam at all three doses was able to attenuate the stress-induced increase in CORT following 5 days of diazepam + restraint treatment. Using the 3.0 mg/kg dose as a probe, it was found that this effect was not dependent on the repeated administration of diazepam, but rather on repeated exposure to restraint. These results suggest that repeated restraint produces a change in neural sensitivity to benzodiazepines. (C) 1997 Elsevier Science Ltd.