Heyman (1983) has suggested that drug-induced changes in schedule- controlled responding reflect separate effects of the drug on motor function and motivation. Some experimental results (see review by Heyman & Monaghan, 1987) indicated that this interpretation of the behavioral action of drugs may help clarify the relation between the behavioral effects and the underlying pharmacodynamics of action of acute drug administration. The proposed experiments will be conducted by selected undergraduate students under the supervision of the PI. The experiments will investigate the development of tolerance to the motoric and motivational effects of d-amphetamine and morphine in laboratory rats responding under random-interval schedules of food presentation. A matching law analysis (Herrnstein, 1970) of the data will yield two derived measures, B/max' which reflects motor performance, and R/half' which reflects reinforcer efficacy. Groups of rats will be subjected to various chronic regimens of drug injections. Tolerance will be assessed by analyzing shifts in the dose response functions for the effects of the drugs on B/max and R/half. The effects of injecting the drugs before or after the behavioral sessions, and the effects of discontinuing the sessions during the periods of chronic dosing will be determined. It is likely that the different drug administration regimens will different- tially affect tolerance development as measured by r/half and b/max. These experiments could clarify some differences between the results of tolerance studies involving drug effects on schedule-controlled operant responding, and the results of studies that look at properties of drugs as discriminative stimuli. The experiments will provide evidence concerning the value of the matching law analyses of drug effects of behavior, and could provide the basis for the development of assay procedures to predict the abuse potential of drugs. Prior to publication, the results will be presented by the student assistants at scientific meetings.
