STIMULUS PROPERTIES OF ANXIOLYTICS IN HUMANS

点击翻译按钮获取中文摘要

The aims of the research proposed in this application are to further delineate behavioral and pharmacological variables that contribute to the reinforcing properties of diazepam and to investigate the discriminative stimulus (DS) properties and subjective effects of diazepam. In previous studies conducted by the Principal Investigator, diazepam has generally not functioned as a positive reinforcer. However, two recent studies showed that its reinforcing properties could be increased under environmental conditions involving administering the drug in multiple doses in a social setting, particularly in participants who had a history of heavier alcohol consumption. Additional preference studies with diazepam are designed to determine the influence of other behavioral and pharmacological variables on diazepam choice. One series of studies will examine the role of divided dosing, pharmacological pretreatment, social facilitation. Further, stimulant drugs (e.g., mazindol) that were not self-administered in previous studies will be evaluated under similar conditions to determine whether the ability to modify reinforcing properties generalizes to other classes of drugs. An additional study will examine the influence of other concurrently available reinforcers on the reinforcing properties of diazepam, both in participants with histories of light and heavier alcohol consumption. The studies on the DS functions of diazepam are an extension of research in which humans were trained to discriminate 10 mg d-amphetamine from placebo. In these trained individuals, it was found that certain anorectic drugs were discriminated as amphetamine whereas anorectics which differed pharmacologically from amphetamine (e.g., fenfluramine) did not. Since a drug from a different pharmacological class also did not substitute, these results indicated that the discrimination was pharmacologically specific. The drug discrimination studies described in the present application are designed to assess the generality of the procedure used to train the amphetamine discrimination by suing diazepam as the training drug and determine: its pharmacological specificity; whether individuals with preexisting characteristics such as anxiety show differences in sensitivity or selectivity; and whether variables such as instructions or behavioral history can modify the DS properties of anxiolytics. Taken together, these two series of studies will increase our understanding of the stimulus functions of anxiolytics related to their dependence potential and therapeutic usefulness as well as provide a more general understanding of environmental influences that modify the stimulus functions of drugs in humans.