A novel-response procedure enhances the selectivity and sensitivity of a triazolam discrimination in humans

Placebo-appropriate responding in drug discrimination can be difficult to interpret because such responding can indicate either the absence of any drug effect or the absence of a specific drug effect. This study addressed the overinclusiveness of placebo-appropriate responding by providing a response alternative for novel-drug effects (i.e., effects unlike the training stimuli). This "novel-response procedure" used instructions that indicated that only responses on a novel-appropriate manipulandum would be reinforced in the presence of novel drug effects. Four healthy male volunteers (ages 19-32) were trained to discriminate 0.32 mg/70 kg of triazolam from placebo. Then, dose-effect curves were determined for triazolam (0.1-0.32 mg/70 kg) and d-amphetamine (5 and 20 mg/70 kg) with a standard two-response procedure (drug vs. placebo) and the novel-response procedure. Triazolam produced dose-related increases in triazolam-appropriate responding with both procedures. d-Amphetamine produced predominantly placebo-appropriate responding with the two-response procedure and predominantly novel-appropriate responding with the novel-response procedure. Unexpectedly, the triazolam dose-effect curve obtained with the novel-response procedure was shifted to the left relative to the two-response procedure for discrimination measures. A similar effect was evident for both the triazolam and d-amphetamine dose-effect curves for some self-report measures. Because of the increased selectivity of placebo-appropriate responding and the increased potency of the drug stimulus, the novel-response procedure may represent a methodological advance for drug discrimination research.