Effects of beta-carboline-ethyl ester on plasma corticosterone--a parallel with antagonist-precipitated diazepam withdrawal.
Effects of beta-carboline-ethyl ester on plasma corticosterone--a parallel with antagonist-precipitated diazepam withdrawal.
复制标题
β-咔啉乙酯对血浆皮质酮的影响——与拮抗剂诱发地西泮戒断平行。
DOI：
10.1016/0024-3205(89)90324-x
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发表时间：
1989
期刊：
影响因子：
6.1
通讯作者：
Johnson,C
中科院分区：
文献类型：
--
作者：
Eisenberg,RM;Johnson,C
地西泮已被证明产生身体依赖性的基础上观察到的行为刺激，或在我们的实验室中，通过增加血浆皮质酮（CS）在拮抗剂沉淀的撤退。行为兴奋似乎类似于β-咔啉酯给药后观察到的兴奋-据报道，该药物与苯二氮卓受体相互作用，称为“反向激动剂”。本研究的重点是将CS变化的发生与其他人先前观察到的行为兴奋相关联。此外，这些研究旨在显示苯二氮卓类药物戒断症状与β-咔啉乙酯药理学作用之间的平行性。实验是在清醒的无拘束雄性Sprague-Dawley大鼠中进行的，使用声音衰减单向视觉盒，带有慢性静脉内导管。这些研究比较了β-咔啉乙酯（βCCE）诱导的大鼠激素和行为变化与CGS-8216诱导的大鼠地西泮戒断8天。长期给予地西泮（5 mg/kg/天）的大鼠在CGS-8216给药后显示血浆（CS）显著增加。行为禁欲评分也显着升高。βCCE（0.5-5.0 mg/kg）可使血浆CS浓度呈剂量依赖性增加。0.5和2.0 mg/kg剂量下的行为评分也有所增加。CGS-8216在1.0和2.0 mg/kg剂量下可拮抗β CCE诱导的血浆CS升高，但在0.5 mg/kg剂量下无拮抗作用。在长期接受地西泮给药的动物中，βCCE诱发的血浆CS升高时间比溶剂给药动物更长，表明存在双重激动剂/拮抗剂效应。这些数据表明，CS升高与戒断期间的行为效应之间存在平行关系，βCCE的作用与戒断表现之间存在相似性。
Diazepam has been shown to produce physical dependence based on observations of behavioral stimulation or, in our laboratory, by increases in plasma corticosterone (CS) during antagonist-precipitated withdrawal. The behavioral excitation appears similar to that observed following the administration of β-carboline esters--agents reported to interact with benzodiazepine receptors and termed “inverse agonists”. The focus of the present study is to correlate the occurrence of changes in CS with behavioral excitation previously observed by others. Further, these studies are designed to show a parallel between the manifestations of benzodiazepine withdrawal and the pharmacologic effects of β-carboline ethyl ester. Experiments were done in conscious unrestrained male Sprague-Dawley rats, with chronic i.v. catheters, using sound-attenuated one-way vision boxes. These studies compared the hormonal and behavioral changes induced by β-carboline ethyl ester (βCCE) with CGS-8216-precipitated withdrawal in rats treated with diazepam for 8 days. Rats treated chronically with diazepam (5 mg/kg/day), showed a significant increase in plasma (CS) following CGS-8216. Behavioral abstinence scores were also significantly elevated. βCCE (0.5–5.0 mg/kg) showed a significant dose-related increase in plasma CS. Behavioral scores were also increased at doses of 0.5 and 2.0 mg/kg. βCCE-induced plasma CS increases were antagonized by CGS-8216 at doses of 1.0 and 2.0 mg/kg but not by 0.5 mg/kg. In animals chronically treated with diazepam, βCCE evoked a more prolonged plasma CS elevation than in vehicle-treated animals suggesting a dual agonist/antagonist effect. These data suggest a parallel between CS elevations and behavioral effects during withdrawal as well as similarities between the action of βCCE and the manifestations of this withdrawal.