Aley K O, Kulkarni S K, Mathur R, Nayar U
Department of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Indian J Exp Biol. 1990 Dec;28(12):1149-59.
Effect of chronic treatment with Ro 15-1788, a benzodiazepine (BZ) receptor antagonist, and its withdrawal, on the cortical and hippocampal electroencephalogram (EEG) was investigated in rats. Chronic treatment with Ro 15-1788 and its withdrawal (24 and 48 hr) were found to reduce the EEG amplitude in both cortical and hippocampal regions. This reduction in cortical and hippocampal EEG amplitude produced by chronic treatment with Ro 15-1788 and its withdrawal was reversed by gamma aminobutyric acid (GABA), pentobarbitone and picrotoxin, agents known to modulate the GABA/BZ synaptic events by acting at different sites on the complex. Baclofen a GABAB agonist and FG7142, a BZ inverse agonist were found to further reduce the EEG amplitude in the cortical and hippocampal regions of these rats, chronically treated with Ro 15-1788. Diazepam, a BZ agonist was found to have no significant effect on the alteration produced in the cortical and hippocampal EEG amplitude by chronic treatment with Ro 15-1788 or its withdrawal. It is suggested that the conformational changes produced on the GABA/BZ receptor complex by BZ receptor occupation, has a facilitatory effect on the actions of those drugs which act on the GABA/BZ receptor complex and the direction of this enhancement depended on the nature of the drug.
研究了苯二氮䓬（BZ）受体拮抗剂Ro 15-1788的长期治疗及其撤药对大鼠皮质和海马脑电图（EEG）的影响。发现Ro 15-1788的长期治疗及其撤药（24小时和48小时）会降低皮质和海马区域的EEG振幅。Ro 15-1788长期治疗及其撤药所导致的皮质和海马EEG振幅降低，可被γ-氨基丁酸（GABA）、戊巴比妥和印防己毒素逆转，这些药物已知可通过作用于复合物的不同位点来调节GABA/BZ突触事件。发现GABAB激动剂巴氯芬和BZ反向激动剂FG7142会进一步降低这些长期接受Ro 15-1788治疗的大鼠皮质和海马区域的EEG振幅。发现BZ激动剂地西泮对Ro 15-1788长期治疗或其撤药所引起的皮质和海马EEG振幅改变无显著影响。研究表明，BZ受体被占据后在GABA/BZ受体复合物上产生的构象变化，对作用于GABA/BZ受体复合物的药物的作用具有促进作用，且这种增强作用的方向取决于药物的性质。
