Stolerman I P, Garcha H S, Rose I C
Psychopharmacology (Berl). 1986;89(2):183-8. doi: 10.1007/BF00310626.
The discriminative stimulus effect of midazolam, a short-acting benzodiazepine, was used for testing the effects of drugs thought to act as antagonists at different sites in the proposed benzodiazepine receptor complex. Rats were trained in a standard two-bar operant conditioning procedure with food reinforcers delivered on a tandem schedule. The 0.4 mg/kg dose of midazolam used for training was well discriminated, typically yielding at least 95% correct responding. The benzodiazepine receptor antagonist Ro 15-1788 blocked the discriminative effect of midazolam but did not influence generalization to pentobarbitone (7.5 mg/kg). The indirect GABA antagonist picrotoxin attenuated both generalization to pentobarbitone and its response rate-reducing effect. Picrotoxin had no effect on the discriminative effect of midazolam at 0.4 mg/kg but it blocked the effect of 0.1 mg/kg. Even in doses which reduced overall response rates, nicotine did not block discrimination of midazolam (0.4 mg/kg). The results are consistent with models which postulate a GABA-linked ion channel which is a site of action for barbiturates and which is "downstream" of the benzodiazepine receptor itself.
短效苯二氮䓬类药物咪达唑仑的辨别刺激效应被用于测试那些被认为在假定的苯二氮䓬受体复合物中不同位点起拮抗剂作用的药物的效果。大鼠在标准双杆操作性条件反射程序中接受训练，食物强化剂按串联时间表给予。用于训练的0.4毫克/千克剂量的咪达唑仑能被很好地辨别出来，通常产生至少95%的正确反应。苯二氮䓬受体拮抗剂Ro 15 - 1788阻断了咪达唑仑的辨别效应，但不影响对戊巴比妥（7.5毫克/千克）的泛化。间接GABA拮抗剂印防己毒素减弱了对戊巴比妥的泛化及其降低反应率的效应。印防己毒素对0.4毫克/千克的咪达唑仑辨别效应没有影响，但它阻断了0.1毫克/千克的效应。即使在降低总体反应率的剂量下，尼古丁也不阻断对0.4毫克/千克咪达唑仑的辨别。这些结果与假设存在一个与GABA相关的离子通道的模型一致，该离子通道是巴比妥类药物的作用位点，并且位于苯二氮䓬受体本身的“下游”。
