Animal models of memory have largely involved the measurement of short-term memory or more precisely working memory. This can be defined as the memory which is required to perform correctly on a given trial. This is different from long-term or reference memory. Reference memory has been defined as that memory which relates the presentation of the stimulus, the response and the presentation of the reinforcing stimulus. These operational definitions are essentially what is known in operant conditioning as stimulus control and schedule control of behavior. Most animal models of short-term or working memory have utilized discrete trial procedures in which each correct behavioral response was reinforced. Such continuous reinforcement of behavior has essentially ignored the influence of schedules of reinforcement on the control of behavior. It is, therefore, not surprising that it has been difficult to know whether the drug was effecting stimulus control (working memory) or schedule control of the behavior (reference memory). This application proposes to examine the effect of the schedule of reinforcement on the effects of drugs of abuse on. memory function. Animal models of working memory, delayed matching-to-sample and delayed alternation, will be programmed under continuous and intermittent schedules of reinforcement. Specifically, delayed matching-to-sample and delayed alternation will be programmed under either a discrete trial (fixed-ratio 1) schedule, or under different second-order schedules (a second-order fixed-ratio 10, a second-order fixed-interval 300 sec, a second-order variable-interval 100 sec, and a second-order fixed-interval 100 sec) in which the unit of behavior is the discrete trial. In addition, two different approaches will be used to examine whether the drug is disrupting stimulus control (working memory) or schedule control (reference memory). The effect of each drug will be determined under both simultaneous matching and delayed matching, and by examining the effects of schedule-induced bias in responding. Finally, the effects of drugs of abuse will be examined as a function of the degree of stimulus control of behavior by different types of events (position vs. visual stimuli or auditory vs. temporal stimuli). It is hoped that these studies will provide additional insights into the effects of drugs of abuse on cognitive function, as well as, provide information on the role of the schedule of reinforcement in the measurement of cognitive function.
