Järbe T U, McMillan D E
Pharmacol Biochem Behav. 1983 Jan;18(1):73-80. doi: 10.1016/0091-3057(83)90254-x.
One group of pigeons (n = 5) was trained to discriminate between the effects induced by 5.6 mg/kg of diazepam (DZP) and the vehicle whereas other pigeons (n = 5) had to discriminate between 3.0 g/kg of ethanol (ETOH) and the vehicle, administered intragastrically (IG) 10 and 40 min prior to the training sessions respectively. Once trained, the pigeons were tested with either diazepam or ethanol alone and in combination. The birds trained to discriminate between DZP and the vehicle mostly performed non-drug associated responses when tested with ETOH (0.56 to 3.0 g/kg). Tests with other doses of DZP (0.3 to 3.0 mg/kg) in the diazepam-trained birds resulted in an ED50 value of 1.4 mg/kg. The birds trained to discriminate between ETOH and the vehicle generalized DZP to ETOH, the ED50 value for diazepam being 3.0 mg/kg. Tests with other doses of ETOH (0.56 to 2.0 g/kg) in this latter group resulted in an ED50 value of 1.3 g/kg. Tests with combinations of DZP and ETOH produced a shift of the dose-response curves to the left indicating drug additivity. The discrimination of 5.6 mg/kg of IG administered DZP but not that of ETOH (3.0 g/kg) was attenuated by injections of the analeptic bemegride (ED50 = 5.5 mg/kg), thus suggesting a difference in the cueing processes of the two drugs. When tested singly, bemegride induced non-drug responding or complete suppression of responding in the birds at the doses of 3.0 and 10.0 mg/kg respectively. In conclusion, the discriminable effects of DZP and ETOH are additive or even supra-additive, but the stimulus properties of the two drugs are not identical.
一组鸽子(n = 5)被训练区分5.6毫克/千克地西泮(DZP)和赋形剂所诱导的效应,而另一组鸽子(n = 5)则必须区分3.0克/千克乙醇(ETOH)和赋形剂,分别在训练前10分钟和40分钟经胃内(IG)给药。一旦训练完成,鸽子分别用单独的地西泮或乙醇以及两者的组合进行测试。训练区分DZP和赋形剂的鸽子在用ETOH(0.56至3.0克/千克)测试时大多表现出与药物无关的反应。用地西泮训练的鸽子用其他剂量的DZP(0.3至3.0毫克/千克)进行测试,得出的半数有效剂量(ED50)值为1.4毫克/千克。训练区分ETOH和赋形剂的鸽子将DZP与ETOH产生了泛化,地西泮的ED50值为3.0毫克/千克。在后者这组鸽子中用其他剂量的ETOH(0.56至2.0克/千克)进行测试,得出的ED50值为1.3克/千克。用地西泮和ETOH组合进行测试使剂量反应曲线向左移动,表明药物具有相加性。注射兴奋药美解眠(ED50 = 5.5毫克/千克)减弱了对5.6毫克/千克经胃内给药的DZP的辨别,但未减弱对ETOH(3.0克/千克)的辨别,因此表明两种药物的提示过程存在差异。单独测试时,美解眠分别在3.0毫克/千克和10.0毫克/千克的剂量下在鸽子中诱导出与药物无关的反应或完全抑制反应。总之,DZP和ETOH的可辨别效应是相加的甚至是超相加的,但两种药物的刺激特性并不相同。