EFFECTS OF DIAZEPAM AND HYDROMORPHONE IN TRIAZOLAM-TRAINED HUMANS UNDER A NOVEL-RESPONSE DRUG DISCRIMINATION PROCEDURE

Seven healthy normal male and female volunteers (21-31 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg, PO; e.g., drug A) and placebo (e.g., drug B) under a three-choice, instructed novel response drug discrimination procedure. Once the criterion for discrimination was met (i.e., >85% correct responding on four consecutive sessions), dose-effect curves were determined for triazolam (0.1-0.56 mg/70 kg), the benzodiazepine diazepam (10-32 mg/70 kg) and the opioid agonist hydromorphone (1-6 mg/70 kg). Subjects met the criterion for discrimination within four to six sessions. Triazolam and diazepam produced dose-related increases in triazolam-appropriate responding and no novel-appropriate responding at any dose tested. In contrast, hydromorphone generally increased novel-appropriate responding in a dose-related manner, with placebo-appropriate responding and some triazolam-appropriate responding at intermediate doses occurring also. Triazolam and diazepam produced qualitatively similar increases on several measures of sedative drug effects; hydromorphone increased ratings of ''like novel'' and sedative-like effects in subjects who discriminated hydromorphone as novel relative to those who did not. These results indicate that the novel response drug discrimination procedure enhances the specificity of the triazolam-placebo discrimination.