Kamien J.B., Bickel W.K., Oliveto A.H., Smith B.J., Higgins S.T., Hughes J.R., Badger G.J.
Department of Psychiatry, University of Vermont, Burlington, VT 05401, USA.
Behav Pharmacol. 1994 Jun;5(3):315-325. doi: 10.1097/00008877-199406000-00009.
Six healthy human volunteers (ages 18 to 24) acquired a triazolam (0.32mg/70kg) vs placebo discrimination under a standard, two-response drug discrimination procedure. Dose-effect curves were then determined for triazolam (0.1-0.56mg/70kg), lorazepam (0.75-3.0mg/70kg) and buspirone (7.5-30mg/70kg) under a novel response procedure that provided a response alternative for drugs unlike triazolam or placebo (i.e. a novel-appropriate response). Triazolam dose-dependently increased triazolam-appropriate responding but did not occasion any novel-appropriate responding. Lorazepam dose-dependently increased triazolam-appropriate responding in four of six subjects, but at least one dose also occasioned novel-appropriate responding in three subjects. Buspirone dose-dependently increased novel-appropriate responding, although three of six subjects also made triazolam-appropriate responses following some dose(s). All three drugs comparably increased self-reported sedation. Self-reported effects did not differentiate triazolam from lorazepam whereas only buspirone increased "bad" self-reports, and did not increase "liking" and "good" self-reports. The results suggest that the novel response procedure enhanced the pharmacological selectivity of human benzodiazepine discrimination and may help interpret partial generalization under two-choice drug discrimination procedures. The results also add to the evidence of a close relationship between the discriminative stimulus and self-reported effects of drugs.
六名健康的人类志愿者（年龄在18至24岁之间）在标准的双反应药物辨别程序下进行了三唑仑（0.32mg/70kg）与安慰剂的辨别。然后，在一种新的反应程序下，确定了三唑仑（0.1 - 0.56mg/70kg）、劳拉西泮（0.75 - 3.0mg/70kg）和丁螺环酮（7.5 - 30mg/70kg）的剂量效应曲线，该程序为不同于三唑仑或安慰剂的药物提供了一种反应选择（即一种新的合适反应）。三唑仑剂量依赖性地增加了与三唑仑相符的反应，但未引发任何新的合适反应。劳拉西泮在六名受试者中的四名中剂量依赖性地增加了与三唑仑相符的反应，但至少有一个剂量在三名受试者中也引发了新的合适反应。丁螺环酮剂量依赖性地增加了新的合适反应，尽管六名受试者中有三名在某些剂量后也做出了与三唑仑相符的反应。所有三种药物都同等程度地增加了自我报告的镇静作用。自我报告的效应无法区分三唑仑和劳拉西泮，而只有丁螺环酮增加了“不良”的自我报告，且未增加“喜欢”和“良好”的自我报告。结果表明，新的反应程序增强了人类苯二氮䓬辨别中的药理学选择性，可能有助于解释二选一药物辨别程序下的部分泛化现象。这些结果也进一步证明了药物的辨别性刺激与自我报告效应之间存在密切关系。
