There is concern about the misuse and abuse of benzodiazepine anxiolytic/sedative drugs which are among the most widely used of all medically prescribed compounds. Caffeine is the single most widely used behaviorally active drug and there is increasing concern that a significant proportion of the population may be at health risk from excessive caffine consumption. Despite the fact that both benzodiazepines and caffine have been periodically identified as being drugs of abuse, the reinforcing and physical dependence producing effects of these compounds remain incompletely characterized. This project will investigate these aspects of benzodiazepines and caffine. In addition to providing specific information about behavioral and pharmacological mechanisms by which benzodiazepines and caffine come to capture and control behavior, this research should provide valuable insights into the general nature of the drug dependence process. A series of studies of baboons and rats is proposed. Two experiments will study environmental conditions which may modulate or enhance the intravenous and oral self-administration of benzodiazepines in baboons. A related experiment will use progressive-ratio schedules of drug self-administration to characterize the relative reinforcing effects of benzodiazepines and barbituates in baboons. Two experiments will characterize spontaneous and precipitated withdrawal in baboons exposed to low chronic doses of the benzodiazepine diazepam. Two other experiments will use baboons and rats to investigate the modulation of benzodiazepine physical dependence and/or tolerance by administration of a benzodiazepine receptor antigonist. The final set of experiments will focus on caffine in baboons. Two experiments will investigate optimal conditions for maintaining maximal intravenous and oral caffine self- administration and one experiment will characterize spontaneous withdrawal effects after high chronic doses of caffine.
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