The objective of research proposed in this request for an ADAMHA RSDA (Level II) is to investigate pharmacological and environmental factors that determine how drugs alter and control behavior. Systematic studies are proposed to investigate the behavioral actions of caffeine and related methylxanthines, of benzodiazepines and novel anxiolytic drugs, and of chronically administered cocaine and phencyclidine. The behavioral actions of methylxanthines will be studied by determining: 1) their effects on schedule-controlled behavior under conditions in which caffeine produces consistent increases in response rate, 2) their effects in combination with metabolically stable analogs of adenosine, which have actions opposing those of methylxanthines at adenosine receptors, and 3) their reinforcing effects under conditions in which caffeine maintains persistent self- administration. The effects of methylxanthines will be compared directly with those of other psychomotor-stimulant drugs including cocaine and amphetamine. The behavioral actions of novel drugs with anxiolytic potential will be studied by determining: 1) their effects under conditions that distinguish antianxiety agents from other pharmacological classes, 2) their effects in combination with benzodiazepine antagonists and full agonists, and 3) their effects in combination with methylxanthines and adenosine agonists, which alter the effects of benzodiazepines in qualitatively different ways. The effects of novel drugs will be compared directly with those of prototypical benzodiazepines and other anxiolytics. The effects of chronically administered cocaine and phencyclidine will be studied by determining: 1) how continuous exposure affects behavior maintained by self- administered drugs and other consequences and 2) how such exposure alters the behavioral effects of drugs that may be used illicitly in conjunction with cocaine or phencyclidine. The proposed studies will provide needed quantitative information about the behavioral effects of drugs used persistently in contemporary society.
