PSYCHOACTIVE DRUGS AND AVERSIVELY-MOTIVATED BEHAVIOR

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Techniques to study the actions of drugs on behavior maintained by negative reinforcement are quite limited at the present time despite the clinical importance of analyzing drug effects which are specific to behavior motivated by stress or fear. The proposed research will elaborate the effects of selected psychoactive drugs on a new baseline schedule involving two concurrently programmed types of negative reinforcement in rats. The new baseline involves a standard shock avoidance schedule programmed on one lever with responses on a second lever producing signaled periods of timeout from avoidance. Preliminary studies have indicated that the baseline is differentially sensitive to the effects of opiate drugs (morphine) and anxiolytic drugs (chlordiazepoxide and alcohol). The proposed studies will permit determination of the extent to which the previously observed drug effects are dependent upon the schedule maintaining the behavior, the pre-drug rate of responding, or the type of event maintaining the behavior. Additional studies will extend the analysis to other drugs including stimulants (amphetamine), antipsychotic agents (chlorpromazine), anesthetics (pentobarbital), and drugs influencing the GABA- benzodiazepine receptor complex (CGS 9896, FG 7142, Ro 15- 1788) as well as other agents. The long term goals of these studies are to increase our knowledge of the neuropharmacological basis of negative reinforcement processes. In addition to the significance of the proposed research for theories involving the links between receptor activity and aversively-motivated behavior, these studies will elaborate a new and highly sensitive baseline for use as a tool in the analysis of new drug effects.