De Boer S F, Van der Gugten J, Slangen J L
Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Pharmacol Biochem Behav. 1991 Jan;38(1):13-9. doi: 10.1016/0091-3057(91)90583-n.
The effects of drugs representing three classes of benzodiazepine (BDZ) receptor-acting agents on circulating corticosterone (CS), noradrenaline (NA) and adrenaline (A) were examined in unstressed rats. Intragastric administration of a single-dose of the inverse agonist 3-carbomethoxy-4-ethyl-6,7-dimethoxy-beta-carboline (DMCM; 10 mg/kg) evoked 15-, 4- and 1.5-fold increases in plasma CS, A and NA, respectively, as compared to control values. The DMCM-induced CS, A and NA rises were completely blocked by combined treatment with the BDZ antagonist flumazenil (Ro 15-1788; 20 mg/kg). Flumazenil given alone did not affect plasma hormone levels. Administration (either intragastrically or intraperitoneally) of a single-dose of the BDZ agonist chlordiazepoxide (CDP; 20 mg/kg) produced a 10- to 15-fold increase in plasma CS but caused no change in plasma NA and A contents. Pretreatment with flumazenil blocked the CDP-elicited release of CS. The findings indicate that the CNS mechanisms controlling pituitary-adrenocortical and sympatho-adrenal outflow under basal conditions are functionally linked to central-type BDZ receptor system(s). Drugs with agonist or inverse-agonist actions at these receptor sites can be differentiated from each other by their distinct effects on plasma NA and A, but not CS, release.
在未受应激的大鼠中，研究了代表三类苯二氮䓬（BDZ）受体作用剂的药物对循环皮质酮（CS）、去甲肾上腺素（NA）和肾上腺素（A）的影响。与对照值相比，单剂量反向激动剂3 - 甲氧羰基 - 4 - 乙基 - 6,7 - 二甲氧基 - β - 咔啉（DMCM；10毫克/千克）经胃内给药后，血浆CS、A和NA分别升高了15倍、4倍和1.5倍。DMCM诱导的CS、A和NA升高可被BDZ拮抗剂氟马西尼（Ro 15 - 1788；20毫克/千克）联合治疗完全阻断。单独给予氟马西尼不影响血浆激素水平。单剂量BDZ激动剂氯氮䓬（CDP；20毫克/千克）经胃内或腹腔内给药后，血浆CS升高了10至15倍，但血浆NA和A含量未发生变化。氟马西尼预处理可阻断CDP引起的CS释放。这些发现表明，在基础条件下控制垂体 - 肾上腺皮质和交感 - 肾上腺流出的中枢神经系统机制在功能上与中枢型BDZ受体系统相关。在这些受体部位具有激动剂或反向激动剂作用的药物可通过它们对血浆NA和A释放的不同影响（而非对CS释放的影响）来相互区分。
