Research efforts in drug discrimination (DD) have been hampered by the lack of specificity in placebo responding; that is, placebo responding is occasioned by both the absence of drug effects and by drug effects unlike the training drug. This lack of specificity impedes understanding of partial generalization and functional antagonism of drug stimuli. Several theoretical interpretations of these phenomena have been proposed. However, experimental verification of these interpretations have been difficult if not impossible. Given that DD is an essential research tool for understanding the pharmacology of a wide range of abused drugs, this continuing difficulty in understanding these frequently observed and investigated phenomena is undesirable and may suggest the limits of this methodology. As part of our progress in studying the discriminative stimulus effects of benzodiazepines in the preceding two years of funding, we have developed a new procedure for use in humans that may resolve these enduring problems of DD research. this procedure established a novel- response alternative for subjects given a drug that is neither like the training drug not like placebo. this procedure has successfully provided a means to distinguish between the presence of a specific drug effect (drug responding), the absence of drug effects (placebo responding), and other drug effects (novel responding). In this proposed project, relevant drugs will be tested under a standard two-response and this new novel-response DD procedure. Occurrences of partial generalization or functional antagonism can be identified in the two-response procedure and the distribution of responding across the three responses in the novel- response procedure would indicate how to interpret them. Thus, this research project will clarify how to interpret these enduring problems. Benzodiazepines will continue to be the drug class under investigation. Benzodiazepines are well suited for this project because their discriminative stimulus effects of benzodiazepines are often less specific than those obtained with other drug classes. Triazolam will continue to be our training drug. Recently, triazolam's untoward effects have been gaining considerable attention. By examining the similarity and differences of triazolam's effects with other agents, this research will provide important information about this current public health concern. Finally, the novel-response procedure will provide new information concerning the similarities and differences of various sedative agents, and new insights into the behavioral pharmacology of benzodiazepines and related compounds. In summary, this proposed competing renewal will employ the novel- response procedure to examine issues of partial generalization and functional antagonism. The results of the proposed research will (1) provide a methodological advance for the growing research area of human DD, (2) provide a clearer interpretation of some current problems of DD research, (3) provide rigorous data about the human pharmacology and abuse liability of benzodiazepines and other sedatives in general and triazolam in particular.
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