EFFECTS OF BENZODIAZEPINE RECEPTOR PARTIAL INVERSE AGONISTS IN THE ELEVATED PLUS-MAZE TEST OF ANXIETY IN THE RAT
EFFECTS OF BENZODIAZEPINE RECEPTOR PARTIAL INVERSE AGONISTS IN THE ELEVATED PLUS-MAZE TEST OF ANXIETY IN THE RAT
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DOI：
10.1007/bf02245598
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发表时间：
1995-09-01
影响因子：
3.4
通讯作者：
JONES, GH
中科院分区：
文献类型：
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作者：
COLE, BJ;HILLMANN, M;JONES, GH
本系列实验研究了五种苯二氮卓受体（BZR）部分逆激动剂对大鼠在高架迷宫中的行为的影响。这些药物在一个标准的正迷宫中进行了测试，在张开的手臂上增加了3厘米的墙壁，因为这已经被证明可以增加正迷宫对类焦虑药物作用的敏感性（Jones和Cole 1995）。检测药物为FG 7142 （0-100 mg/kg）、β - cce （0-30 mg/kg）、2K 132 556 （0-100 mg/kg）、ZK 90 886 （0-30 mg/kg）和Ro 15-4513 （0-30 mg/kg）。为了与以前的研究进行比较，还研究了三种对照物质的影响，即DMCM （0-2.5 mg/kg）、戊四氮（PTZ; 0-30 mg/kg）和育亨宾（0-5 mg/kg）。这三种对照化合物产生了剂量依赖性的开放臂探索持续时间和开放臂进入总次数的减少，表明了类似焦虑的作用。DMCM剂量为1.25和2.5 mg/kg， PTZ剂量为30 mg/kg，育亨宾剂量为5 mg/kg时产生显著影响。BZR部分逆激动剂FG 7142（10、30和100 mg/kg）也减少了开放臂探查的持续时间和进入臂的总次数。最小有效剂量导致受体占用约80%。Ro 15-4513也产生类似焦虑的作用，但仅在剂量（30 mg/kg）时导致受体占用约95%。相比之下，其他BZR部分逆激动剂，ZK 132 553和ZK 90 886，即使在产生大于95%受体占用的剂量下，也没有显著缩短张开臂探查的持续时间。在任何剂量下（0-30 mg/kg）， β - cce也没有减少张开臂探查。GABA位移是一种内在活性的生化指标，表明后三种化合物比Ro 15-4513具有更强的拮抗作用。综上所述，这些结果表明，并非所有的BZR受体部分逆激动剂在大鼠+迷宫中都具有类似焦虑的活性，并且GABA位移这一内在功效的生化指标并不能预测哪些BZR部分逆激动剂具有焦虑性。
The present series of experiments examined the effects of five benzodiazepine receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to the open arms, as this has been shown to increase the sensitivity of the plus maze to anxiogenic-like drug effects (Jones and Cole 1995). The drugs tested were FG 7142 (0-100 mg/kg), beta-CCE (0-30 mg/kg) 2K 132 556 (0-100 mg/kg), ZK 90 886 (0-30 mg/kg) and Ro 15-4513 (0-30 mg/kg). to allow a comparison with previous studies, the effects of three reference substances, DMCM (0-2.5 mg/kg), pentylenetetrazol (PTZ; 0-30 mg/kg) and yohimbine (0-5 mg/kg), were also examined. These three reference compounds produced a dose-dependent reduction in the duration of open arm exploration and the total number of open arm entries, indicative of anxiogenic-like effects. DMCM produced significant effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5 mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also reduced the duration of open arm exploration and the total number of arm entries. The minimally effective dose resulted in a receptor occupancy of approximately 80%. Ro 15-4513 also produced anxiogenic-like effects, but only at a dose (30 mg/kg) that resulted in a receptor occupancy of approximately 95%. In contrast, the other BZR partial inverse agonists, ZK 132 553 and ZK 90 886, did not significantly reduce the duration of open arm exploration, even at doses that produced greater than 95% receptor occupancies. beta-CCE also did not reduce open arm exploration at any dose tested (0-30 mg/kg). The GABA shift, a biochemical index of intrinsic activity, indicates that these latter three compounds are more inverse agonistic than Ro 15-4513. In summary, these results demonstrate that not all BZR receptor partial inverse agonists have anxiogenic-like activity in the rat plus maze, and that the GABA shift, a biochemical index of intrinsic efficacy, does not predict which BZR partial inverse agonists are anxiogenic.