Concas A, Corda M G, Biggio G
Brain Res. 1985 Aug 19;341(1):50-6. doi: 10.1016/0006-8993(85)91471-4.
The cerebral cortices of rats habituated to the handling manipulation that precedes sacrifice by guillotine (unstressed rats) have a higher number of low affinity GABA receptors than naive rats (stressed rats). Foot shock stress delivered to handling-habituated rats 5 min before sacrifice decreased the number of low affinity GABA receptors to the level found in naive animals, while leaving almost unchanged the [3H]GABA binding in the latter group. Since benzodiazepine (BZ) recognition sites are the target through which benzodiazepines modulate the emotional states of the animals, we investigated whether these receptors were involved in the action of foot shock stress on GABA binding. The in vitro addition of diazepam (5 X 10(-6) M) to cortical membranes from foot-shocked handling-habituated rats brought back the number of low affinity GABA receptors to the level found in cortical membranes from handling habituated rats. Moreover, the effect of foot shock on low affinity GABA receptors was completely antagonized in vivo by pretreatment with the specific benzodiazepine antagonist Ro15-1788 (30 mg/kg per os). Since the effect of foot shock on [3H]GABA binding is mimicked by the in vitro addition of beta-carbolines to cortical membranes from handling habituated rats, our working hypothesis is that an endogenous ligand for BZ recognition sites, possessing beta-carboline-like properties, is released during foot shock stress.
习惯断头处死前的抓握操作的大鼠(未应激大鼠)的大脑皮质,其低亲和力γ-氨基丁酸(GABA)受体数量比未经处理的大鼠(应激大鼠)更多。在处死前5分钟对习惯抓握的大鼠施加足部电击应激,可使低亲和力GABA受体数量降至未经处理动物的水平,而后者组中的[³H]GABA结合几乎未变。由于苯二氮䓬(BZ)识别位点是苯二氮䓬调节动物情绪状态的靶点,我们研究了这些受体是否参与足部电击应激对GABA结合的作用。将地西泮(5×10⁻⁶ M)体外添加到足部电击习惯抓握大鼠的皮质膜中,可使低亲和力GABA受体数量恢复到习惯抓握大鼠皮质膜中的水平。此外,在体内用特异性苯二氮䓬拮抗剂Ro15 - 1788(30 mg/kg口服)预处理,可完全拮抗足部电击对低亲和力GABA受体的影响。由于在习惯抓握大鼠的皮质膜中体外添加β-咔啉可模拟足部电击对[³H]GABA结合的作用,我们的工作假设是,在足部电击应激期间,会释放一种具有β-咔啉样特性的BZ识别位点内源性配体。