Shannon H E, Holtzman S G
J Pharmacol Exp Ther. 1977 Apr;201(1):55-66.
Rats were trained in a two-choice discrete trial avoidance paradigm to discriminate between saline and 3.0 mg/kg of morphine. Behavior was considered to be under stimulus ocntrol when the rats completed at least 90% of the trials in a 20-trial session on the morphine-appropriate choice lever after receiving morphine and when they completed at least 90% of the trials on the saline-appropriate choice lever after receiving saline. The discriminative effects of morphine, measured by responding on the morphine-appropriate lever, were then evaluated by determining the dose-response characteristics of representative narcotic analgesics, analgesics with mixed agonist and narcotic antagonist properties and nonopioid psychoactive drugs. Eight narcotic analgesics each produced dose-related responding on the morphine-appropriate lever. The relative potency for producing discriminative effects equivalent to those produced by 3.0 mg/kg of morphine ranged form etonitazene = 1000 x morphine to propoxyphene = 0.0175 x morphine. Of the narcotic antagonist analgesics tested, butorphanol and nalmexone produced discriminative effects equivalent to those of the morphine training dose whereas nalorphine, levallorphan, oxilorphan, nalbuphine and ketocyclazocine did not. The nonopioid psychoactive drugs, mescaline, ketamine, physostigmine and scopolamine, also failed to produce discriminative effect equivalent to those produced by 3.0 mg/kg of morphine. These results confirm and extend our previous findings that of those drugs which have also been evaluated in man, discriminative effects equivalent to the training dose of morphine are produced uniquely by narcotic analgesics and narcotic antagonists which produce morphine-like subjective effects. These results are compatible with the hypothesis that the properties of morphine which enable it to function as a discriminative stimulus in the rat are analogous to those responsible for producing subjective effects in man.
将大鼠置于双选择离散试验回避范式中进行训练，以区分生理盐水和3.0毫克/千克的吗啡。当大鼠在注射吗啡后，在20次试验的一个时段内，至少90%的试验选择了与吗啡对应的杠杆，并且在注射生理盐水后，至少90%的试验选择了与生理盐水对应的杠杆时，行为被认为处于刺激控制之下。然后，通过确定代表性麻醉性镇痛药、具有混合激动剂和麻醉拮抗剂特性的镇痛药以及非阿片类精神活性药物的剂量-反应特性，来评估吗啡通过对与吗啡对应的杠杆的反应所测量的辨别效应。八种麻醉性镇痛药各自在与吗啡对应的杠杆上产生了剂量相关的反应。产生与3.0毫克/千克吗啡等效辨别效应的相对效价范围从依托尼嗪=1000×吗啡到丙氧芬=0.0175×吗啡。在所测试的麻醉拮抗剂镇痛药中，布托啡诺和纳美酮产生的辨别效应与吗啡训练剂量的效应相当，而烯丙吗啡、左洛啡烷、羟吗啡酮、纳布啡和环唑辛则没有。非阿片类精神活性药物，如三甲氧苯乙胺、氯胺酮、毒扁豆碱和东莨菪碱，也未能产生与3.0毫克/千克吗啡等效的辨别效应。这些结果证实并扩展了我们先前的发现，即在人类中也进行过评估的那些药物中，只有产生吗啡样主观效应的麻醉性镇痛药和麻醉拮抗剂才能产生与吗啡训练剂量等效的辨别效应。这些结果与以下假设一致，即吗啡在大鼠中能够作为辨别性刺激发挥作用的特性类似于在人类中产生主观效应的特性。
