White J-A.W., Stolerman I.P.
Department of Psychiatry, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK.
Behav Pharmacol. 1994 Jun;5(3):351-355. doi: 10.1097/00008877-199406000-00013.
Rats were trained to discriminate nicotine (0.4mg/kg s.c.), midazolam (0.2mg/kg s.c.) or the combination of these drugs from saline (n = 10). The rats were trained to 95% accuracy in a two-bar operant procedure with a tandem schedule of food reinforcement. Testing with the individual drugs in the mixture-trained group showed that nicotine (85% drug-appropriate responding) was a more salient component than midazolam (47%) in the compound stimulus. The rats were tested with benzodiazepine and nicotine antagonists individually and in combination (mecamylamine 0.2-1.6mg/kg s.c.; flumazenil 2.5-20mg/kg i.p.). Results for the mixture-trained animals showed that flumazenil had no effect on its own, however mecamylamine on its own produced a significant but incomplete block in doses of 0.4-1.6mg/kg. The greater salience of the nicotine component of the cue would explain the block by mecamylamine but not flumazenil. The antagonists in combination produced greater blockade than mecamylamine on its own. The selectivity of the antagonist actions on the different cue components was also demonstrated. The results suggest that in drug discrimination experiments, "false negative" results may be obtained with antagonists when a training drug produces a stimulus with more than one component.
将大鼠训练以区分尼古丁（皮下注射0.4mg/kg）、咪达唑仑（皮下注射0.2mg/kg）或这些药物与生理盐水的组合（n = 10）。采用双杆操作程序并结合食物强化的串联时间表，将大鼠训练至95%的准确率。对混合训练组的大鼠进行单独药物测试，结果显示在复合刺激中，尼古丁（85%的药物适应性反应）比咪达唑仑（47%）更显著。分别用苯二氮䓬和尼古丁拮抗剂以及它们的组合对大鼠进行测试（美加明皮下注射0.2 - 1.6mg/kg；氟马西尼腹腔注射2.5 - 20mg/kg）。混合训练动物的测试结果显示，氟马西尼单独使用无作用，然而美加明单独使用在剂量为0.4 - 1.6mg/kg时产生显著但不完全的阻断作用。线索中尼古丁成分的更高显著性可以解释美加明的阻断作用，而不能解释氟马西尼的作用。拮抗剂组合产生的阻断作用比美加明单独使用时更大。还证明了拮抗剂对不同线索成分作用的选择性。结果表明，在药物辨别实验中，当训练药物产生具有多个成分的刺激时，拮抗剂可能会得出“假阴性”结果。
