Comparing single and cumulative dosing procedures in human triazolam discriminators.

This study evaluated a cumulative dosing procedure for drug discrimination with human participants. Four participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. A crossover design was used to compare the results under a single dosing procedure with results obtained under a cumulative dosing procedure. Under the single dosing procedure, a dose of triazolam (0, 0.05, 0.15, or 0.35 mg/70 kg) or secobarbital (0, 25, 75, or 175 mg/70 kg) was administered 45 min before assessment. Determining each dose-effect curve thus required four sessions. Under the cumulative dosing procedure, four doses of triazolam (0, 0.05, 0.10, and 0.20 mg/70 kg) or secobarbital (0, 25, 50, and 100 mg/70 kg) were administered approximately 55 min apart, producing a complete dose-effect curve in one four-trial session. Regardless of procedure, triazolam and secobarbital produced discriminative stimulus and self-reported effects similar to previous single dosing studies in humans. Shifts to the right in cumulative dose-effect curves compared to single dose-effect curves occurred on several self-report measures. When qualitative stimulus functions rather than quantitative functions are of interest, application of cumulative dosing may increase efficiency in human drug discrimination.     

Emergent equivalence relations between interoceptive (drug) and exteroceptive (visual) stimuli.

Conditional "if-then" relations between drug (interoceptive) stimuli and visual (exteroceptive) stimuli were taught to 4 normal humans. Interoceptive stimuli were the effects produced by 0.32 mg/70 kg triazolam (a prototypical benzodiazepine) and placebo (lactose-filled capsules); exteroceptive stimuli were black symbols on white flash cards. Following the training of the prerequisite conditional relations, tests of emergent relations were conducted between exteroceptive stimuli and between interoceptive and exteroceptive stimuli. Equivalence relations emerged immediately without explicit training for all 4 subjects. Accuracy of responding during the interoceptive-exteroceptive equivalence tests and subjects' self-reports showed consistent discrimination between the drug effects of triazolam and placebo. Finally, a generalization test assessed whether a novel visual stimulus presented in the context of the placebo (i.e., no drug) would generalize to visual stimuli belonging to the placebo stimulus class. All 3 subjects who completed this test reliably chose the visual stimuli belonging to the placebo class and not the visual stimuli belonging to the triazolam stimulus class. The development of equivalence relations between interoceptive and exteroceptive stimuli demonstrates that private and public stimulus events can emerge as members of the same equivalence class. Theoretical and clinical implications are discussed.     

The effects of diazepam and triazolam on repeated acquisition and performance of response sequences with an observing response.

Drugs often disrupt the acquisition of new response sequences at doses that fail to disrupt the performance of a previously acquired response sequence. This selective drug effect may result from differences in the control exerted by the stimuli presented after each response in the acquisition and performance sequences. To examine the function of these stimuli, an observing procedure was incorporated into a multiple schedule of repeated acquisition and performance of response sequences, in which stimulus presentations were contingent upon an observing response. Three experiments were conducted with humans. Experiment 1 compared responding with and without the observing contingency. No difference was found in the overall percentage of errors across the two conditions. Within the observing condition, observing behaviour was maintained in the acquisition component as long as errors occurred, but was not maintained in the performance component. Experiment 2 examined whether a contingency that increased errors also would increase observing in both the acquisition and performance components. Specifically, reinforcer delivery in each component was contingent upon emitting 10 correct responses and one, two, or four errors. Observing responses increased in the acquisition component as the error requirement increased, whereas observing responses in the performance component increased only when the error requirement was four. Experiment 3 assessed the effects of diazepam (0, 7.5, 15, and 30 mg/70 kg, p.o.) and triazolam (0, 0.375, and 0.75 mg/70 kg, p.o.) on repeated acquisition and performance baselines with the observing contingency. Selective drug effects were obtained in this modified procedure; that is, the percentage of errors in the acquisition component increased at doses that failed to affect the percentage of errors in the performance components. Importantly, drug effects were selective, even though observing responses were not emitted in the performance component and, hence, the stimulus presentations did not occur in that component. These findings suggest that alternative explanations for these differential effects are needed; in that regard, a response-unit account of the selective drug effects is discussed.