Gardner C R
Roussel Laboratories, Swindon, Wiltshire, England.
Pharmacol Biochem Behav. 1989 Dec;34(4):711-5. doi: 10.1016/0091-3057(89)90263-3.
Rats were trained to discriminate either CL218872 (5 mg/kg PO) or chlordiazepoxide (5 mg/kg PO) from vehicle in a 2-lever discrimination task on an FR20 schedule. The discriminative cues produced by these two drugs generalised to a range of benzodiazepine receptor agonists and partial agonists. Nitrazepam, diazepam, RU32698 and RU32514 were less potent in substituting for the CL218872 cue than the chloridiazepoxide cue. Zopiclone, RU31719 and RU43028 substituted for both cues with similar potency, whilst zolpidem and CL218872 were clearly more potent in substituting for the CL218872 cue. Chlordiazepoxide substituted only partially for the CL218872 cue, even at doses which decreased the rate of responding. CGS9896 substituted partially for both cues, but was less effective with the CL218872 cue. RU39419 substituted for the chlordiazepoxide cue, but antagonised the CL218872 cue. CGS8216 and FG7142 antagonised both cues. The contributions of benzodiazepine receptor subtypes or partial agonism to the generation of the CL218872 cue is discussed.
在固定比率20的实验安排下,训练大鼠在双杠杆辨别任务中区分氯普唑仑(CL218872,5毫克/千克口服)或氯氮卓(5毫克/千克口服)与溶媒。这两种药物产生的辨别性线索可泛化至一系列苯二氮䓬受体激动剂和部分激动剂。硝西泮、地西泮、RU32698和RU32514替代氯普唑仑线索的效力低于替代氯氮卓线索的效力。佐匹克隆、RU31719和RU43028以相似效力替代两种线索,而唑吡坦和氯普唑仑在替代氯普唑仑线索方面明显更有效。即使在降低反应率的剂量下,氯氮卓也只能部分替代氯普唑仑线索。CGS9896可部分替代两种线索,但对氯普唑仑线索的效果较差。RU39419替代氯氮卓线索,但拮抗氯普唑仑线索。CGS8216和FG7142拮抗两种线索。本文讨论了苯二氮卓受体亚型或部分激动作用对氯普唑仑线索产生的作用。