This study is a continuation of our assessment of the discriminative stimulus effects of flumazenil, a benzodiazepine receptor antagonist. That study demonstrated that flumazenil (0.56 mg/70 kg) is readily discriminated from saline. In addition, substitution tests with various doses of flumazenil (0, 0.10, 0.32 and 1.0 mg/70 kg) demonstrated dose- dependent increases on several self-report measures sensitive to sedative- like effects (e.g., PCAG subscale of the ARCI, sedative rating on the adjective rating scale) in the 6 subjects who completed the study. This study is being conducted in order to determine whether the observed agonist effects of flumazenil are benzodiazepine-like by training a flumazenil (0.56 mg/70 kg) versus saline discrimination and then conducting substitution tests with three test doses of midazolam (1.0, 1.8, and 3.2 mg/70 kg). The substitution tests are being conducted under a novel-response drug discrimination procedure, which offers subjects a response alternative appropriate for effects unlike flumazenil or saline. Self-reported effects of flumazenil and midazolam are also being compared. In addition, we are testing one dose of caffeine (75 mg/70 kg) as a negative control. Three subjects have completed this study. Thus far, results indicate that flumazenil and midazolam have similar, but not identical, discriminative stimulus effects in humans.
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