The application of drug discrimination (DD) procedures to human subjects has been successful with stimulant and opioid drugs. These discriminations are orderly, pharmacologically specific, and are consistent with findings from non-human studies. Additionally, these studies typically show concordance between DD measures and self-reports of drug effect. Despite their widespread use and abuse, benzodiazepines (BZD) and other sedative hypnotics have yet to be investigated in the human DD paradigm. This project will develop a behavioral DD paradigm for laboratory use with humans and will use this paradigm to comparatively evaluate the discriminative stimulus characteristics of BZD and other sedative hypnotics. Ultimately, the usefulness of this paradigm will be determined by its pharmacologic specificity; that is, a highly specific discrimination will permit careful characterizations of the similarities and differences between BZD and other sedative-hypnotic compounds, while a drug-specific or a non-specific discrimination would have limited usefulness in this regard. In this project, the specificity of the discrimination will be determined by employing progressively more stringent tests across six studies. Study 1 will first develop the procedure and, if necessary, manipulate dose, drug, instructions and the number of training sessions to establish a discrimination between triazolam and placebo. This study will then test whether d-amphetamine is labeled as triazolam or placebo and, thus, establish whether the trained discrimination is more specific than a drug vs. no-drug discrimination. Studies 2-4 will test whether amitriptyline, buspirone, hydromorphone, pentazocine, phenobarbital and secobarbital will be labeled as triazolam or placebo and, thus, establish whether the discrimination is more specific than a sedative vs. nonsedative discrimination. Studies 5-6 will test whether chlordiazepoxide, clonazepam, diazepam, and lorazepam will be labeled as triazolam and, thus, establish whether the discrimination is drug specific. Overall, this project will thoroughly characterize the specificity of the trained discrimination and determine its utility for the study of BZD pharmacology. Additionally, the concordance between, DD and self-reports measures will be examined and, thus, test the widely held assumption that these measures are comparable. The development of a human DD procedure for studying BZD will provide an empirical tool to 1) examine the interoceptive stimulus effects of BZD and how these effects vary across different drugs, doses, populations and situations, 2) understand the neuropharmacology of BZD effects in humans, and 3) screen new anxiolytic, hypnotic, and anticonvulsant drugs for abuse liability.
Showing the most recent 10 out of 13 publications
