FOOT-SHOCK STRESS AND ANXIOGENIC BETA-CARBOLINES INCREASE T-[S-35]BUTYLBICYCLOPHOSPHOROTHIONATE BINDING IN THE RAT CEREBRAL-CORTEX, AN EFFECT OPPOSITE TO ANXIOLYTICS AND GAMMA-AMINOBUTYRIC ACID MIMETICS
FOOT-SHOCK STRESS AND ANXIOGENIC BETA-CARBOLINES INCREASE T-[S-35]BUTYLBICYCLOPHOSPHOROTHIONATE BINDING IN THE RAT CEREBRAL-CORTEX, AN EFFECT OPPOSITE TO ANXIOLYTICS AND GAMMA-AMINOBUTYRIC ACID MIMETICS
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DOI：
10.1111/j.1471-4159.1988.tb01170.x
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发表时间：
1988-12-01
影响因子：
4.7
通讯作者：
BIGGIO, G
中科院分区：
文献类型：
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作者：
CONCAS, A;SERRA, M;BIGGIO, G
本文研究了足部电击应激对t-[35S]-二环磷硫酸丁酯([35S]-TBP)与新鲜大鼠大脑皮层未清洗膜制剂结合的影响，并与GABAA受体激动剂和拮抗剂以及GABAA能传递的正负调节剂进行了比较。[35S]与非应激大鼠相比，足底电击暴露大鼠大脑皮层Tbps结合量增加。Scatchard分析表明，足部电击的影响是由于[35S]Tbps结合位点总数的增加。相反，体外加入蝇草酚或GABA可剂量依赖性地抑制[35S]Tbps的结合，而同时加入GABA受体拮抗剂荷包牡丹碱可使[35S]Tbps结合增加73%。因此，荷包牡丹碱与胁迫类似，在相同的膜制剂中增加了[35S]Tbps的结合。与应激相反，GABA能传递的抗焦虑和正向调节剂(ZK 93423、ZK 91296和安定)以浓度依赖的方式抑制[35S]Tbps的特异性结合。在30微米时，ZK 93423的抑制作用最强(对照的31%)，其次是安定(对照的54%)和部分激动剂ZK 91296(对照的61%)。Scatchard图分析表明，ZK 93423和地西潘的抑制作用是由于[35S]Tbps识别位点密度降低所致。另一方面，引起焦虑的β-碳水化合物DMCM和FG7142模拟了压力的影响。因此，在10微米浓度下，DMCM和FG 7142分别使[35S]Tbps结合量增加22%和25%。苯二氮卓类受体拮抗剂Ro 15-1788和ZK 93426可阻断ZK 93423、ZK 91296和安定的抑制作用和FG 7142和DMCM的兴奋作用。与GABA受体拮抗剂荷包牡丹碱和引起焦虑的β-卡波林相似，而与GABA激动剂、抗焦虑的β-卡波林和苯二氮卓相反，应激增加了大鼠大脑皮层的[35S]Tbps结合，这表明与应激和焦虑相关的一些情绪状态可能是由于GABA-AA/苯二氮卓类受体/氯离子载体复合体水平上的GABA能传递减弱所致。
The effect of foot-shock stress on t-[35S]-butylbicyclophosphorothionate ([35S]TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of GABAA receptor agonists and antagonists and to positive and negative modulators of the GABAergic transmission. [35S]TBPS binding was increased in the cerebral cortex of rats exposed to foot shock compared to that of nonstressed rats. Scatchard analysis revealed that the effect of foot shock was due to an increase in the total number of [35S]TBPS binding sites. In contrast, the in vitro addition of muscimol or GABA induced a dose-dependent inhibition of [35S]TBPS binding, an effect abolished by the concomitant addition of the GABA receptor antagonist, bicuculline, which, per se, enhanced [35S]TBPS binding by 73%. Thus, bicuculline, similar to stress, increased [35S]TBPS binding in the same membrane preparation. In contrast to stress, the anxiolytic and positive modulators of the GABAergic transmission (ZK 93423, ZK 91296 and diazepam) inhibited the specific binding of [35S]TBPS in a concentration-dependent manner. The greatest inhibitory effect was produced by ZK 93423 at 30 .mu.M (31% of control), followed by diazepam (54% of control) and by the partial agonist ZK 91296 (61% of control). Scatchard plot analysis indicated that the inhibition induced by ZK 93423 and diazepam was due to a decrease in the density of [35S]TBPS recognition sites. On the other hand, the anxiogenic .beta.-carbolines DMCM and FG 7142 mimicked the effect of stress. Thus, at a 10 .mu.M concentration, DMCM and FG 7142 increased [35S]TBPS binding by 22% and 25%, respectively. The inhibitory effect of ZK 93423, ZK 91296, and diazepam and the stimulatory effect of FG 7142 and DMCM were blocked by the benzodiazepine receptor antagonists Ro 15-1788 and ZK 93426. The demonstration that stress, similar to the GABA receptor antagonist bicuculline and to anxiogenic .beta.-carbolines and opposite to GABA agonists, anxiolytic .beta.-carbolines, and benzodiazepines, increases [35S]TBPS binding in the rat cerebral cortex, suggests that some emotional state related to stress and anxiety may result from a diminished GABAergic transmission at the level of the GABAA/benzodiazepine receptor/chloride ionophore complex.