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地西泮和苯二氮䓬类拮抗剂CGS 8216对生长抑素能神经元系统的影响。

The effect of diazepam and the benzodiazepine antagonist CGS 8216 on the somatostatinergic neuronal system.

作者信息

Martínez A, Arilla E

机构信息

Department of Biochemistry and Molecular Biology, Medical School, University of Alcalá, Alcalá de Henares, Madrid, Spain.

出版信息

Neuropharmacology. 1993 Apr;32(4):393-9. doi: 10.1016/0028-3908(93)90162-v.

DOI:10.1016/0028-3908(93)90162-v
PMID:8098864
Abstract

The effects of the benzodiazepines and somatostatin (SS) on learning and memory are the opposite of each other. To investigate a possible relationship between these two components, the effects of the administration over time of diazepam and of a benzodiazepine antagonist, 2-phenylpyrazolo [3,4-c]-quinolin-3(5H)-one (CGS 8216), on the levels of somatostatin-like immunoreactivity (SSLI) and on the binding of [125I]Tyr11-somatostatin were studied in the hippocampus of the Wistar rat. Diazepam (5 mg/kg/day, i.p.) and CGS 8216 (20 mg/kg/day, i.p.) did not affect SSLI in the hippocampus, at the three times studied (3, 7 or 14 days). Administration of diazepam for 3 or 7 days decreased the number of somatostatin receptors in synaptosomes from the hippocampus, without influencing their apparent affinity. This decrease could be blocked by concomitant administration of CGS 8216, whereas CGS 8216 alone had no observable effect. After 2 weeks of daily injections of diazepam the levels of binding of somatostatin in the hippocampus returned to control values, coinciding with the tolerance that develops to chronically-administered benzodiazepine agonists. These results suggest that somatostatin receptors might be regulated by benzodiazepine receptors and perhaps may also play a role in some of the behavioural effects of the benzodiazepines.

摘要

苯二氮䓬类药物和生长抑素(SS)对学习和记忆的影响截然相反。为研究这两种成分之间可能存在的关系,在Wistar大鼠海马中研究了随着时间推移给予地西泮和一种苯二氮䓬类拮抗剂2-苯基吡唑并[3,4-c]-喹啉-3(5H)-酮(CGS 8216)对生长抑素样免疫反应性(SSLI)水平以及[125I]酪氨酸11-生长抑素结合的影响。在所研究的三个时间点(3天、7天或14天),地西泮(5毫克/千克/天,腹腔注射)和CGS 8216(20毫克/千克/天,腹腔注射)均未影响海马中的SSLI。给予地西泮3天或7天可减少海马突触体中生长抑素受体的数量,但不影响其表观亲和力。这种减少可被同时给予CGS 8216所阻断,而单独给予CGS 8216则无明显作用。每日注射地西泮2周后,海马中生长抑素的结合水平恢复到对照值,这与长期给予苯二氮䓬类激动剂所产生的耐受性相一致。这些结果表明,生长抑素受体可能受苯二氮䓬受体调节,并且可能在苯二氮䓬类药物的某些行为效应中也起作用。

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