β-Carbolines with agonistic and inverse agonistic properties at benzodiazepine receptors of the rat
β-Carbolines with agonistic and inverse agonistic properties at benzodiazepine receptors of the rat
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对大鼠苯二氮卓受体具有激动和反激动特性的 β-咔啉
DOI：
10.1016/0304-3940(84)90535-4
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发表时间：
1984
影响因子：
2.5
通讯作者：
R. Schmiechen
中科院分区：
文献类型：
--
作者：
D. Stephens;W. Kehr;H. Schneider;R. Schmiechen
在接受训练的大鼠中评估了5种β-咔啉类药物的致焦虑或抗焦虑特性，这些大鼠在两个杠杆操作室中接受训练，当用训练药物处理时，操作一个杠杆以获得食物奖励，而当用盐水处理时，操作另一个杠杆以获得食物奖励。使用了两种这样的药物辨别试验，采用利血平（CDP）或戊四氮（PTZ）作为训练药物。苯二氮卓类（BZ）激动剂ZK 93 423替代CDP线索并拮抗PTZ线索。反向激动剂DMCM和FG 7142显示相反的作用。拮抗剂，ZK 93 426，拮抗CDP线索，但没有取代PTZ，而部分激动剂被确定为CDP样，但只有部分拮抗PTZ线索。抗焦虑谱（CDP替代和PTZ拮抗）与GABA比值约为2相关，而抗焦虑谱与GABA比值小于1相关。拮抗剂和部分激动剂显示中间值。这些观察结果通常与β-咔啉类通过其对影响GABA能神经传递的BZ受体的活性调节焦虑一致。
The anxiogenic or anxiolytic properties of five β-carbolines were assessed in rats trained in two-lever operant chambers to operate one lever to obtain food reward when treated with a training drug, and the other when treated with saline. Two such drug-discrimination tests were used, employing either chlordiazepoxide (CDP) or pentylenetetrazol (PTZ) as training drugs. The benzodiazepine (BZ) agonist, ZK 93 423, substituted for the CDP cue and antagonized the PTZ cue. The inverse agonists DMCM and FG 7142 showed the opposite effects. An antagonist, ZK 93 426, antagonized the CDP cue but did not substitute for PTZ, while a partial agonist was identified as CDP-like but only partially antagonized the PTZ cue. An anxiolytic profile (substitution for CDP and antagonism of PTZ) was associated with GABA ratios of about 2, and an anxiogenic profile with GABA ratios less than 1. The antagonist and partial agonist displayed intermediate values. These observations are generally consistent with the β-carbolines modulating anxiety through their activity at BZ receptors influencing GABAergic neurotransmission.