The proposed experiments will compare the importance of behavioral conditioning factors in the development of tolerance to two anxiolytic drugs, diazepam and midazolam. Tolerance to the sedative effects of these compounds is an integral factor in the abuse and clinical use of sedatives. Widely available midazolam and diazepam have been selected for comparison because of the known difference in duration of action which has been implicated in both processes of drug tolerance and withdrawal. Dose of drug administered will be examined as an important variable in the relationship between conditioning factors and tolerance to midazolam. Special emphasis will be placed on the process of how conditioning factors affect tolerance development and withdrawal characteristics rather than merely observing the existence of conditioning factors. A comprehensive description of behavioral tolerance to these anxiolytics will be accomplished by evaluating response rates, duration of responses, interresponse times, and the force of the responses under various schedules of operant performance. Further delineation of tolerance and withdrawal processes which are important in the repetitive use of these drugs will have implications for the treatment of abusers and in the use of these compounds to treat opiate, cocaine and alcohol abuse.
