This is a request for continued support of an ADAMHA Research Scientist Award. The long-term objectives and specific aims of the proposed research focus upon the development of generalizable knowledge relevant to the environmental and behavioral determinants of drug-seeking and drug-taking as these processes bear upon public health concerns related to drug dependence and abuse. More specifically, the proposed investigations will emphasize experimental studies of the reinforcing, discriminative, and physiological dependence-producing properties of drugs of abuse in laboratory primates with particular reference to the most commonly abused sedative/hypnotic/anxiolytic and stimulant agents (e.g., benzodiazepines, amphetamines, cocaine). Both intravenous and oral routes of administration will be studied and molecular mechanisms of action will be investigated. Investigations will also be undertaken to determine the acute and chronic effects upon sensory and motor functions of such drugs of abuse both singly and in combination so as to develop an appropriate behavioral toxicity data base in laboratory primates. These studies will involve applications and extensions of animal psychophysical methods for assessment of drug effects upon auditory and visual thresholds, reaction times, and vowel discrimination functions. Studies will also be undertaken to explore the determinants and consequences of drug-seeking and drug-taking in human volunteers within the context of a continuously programmed residential laboratory for the experimental analysis of small scale social systems with particular emphasis upon the motivational and performance effects of abused substances (e.g. marijuana) under such conditions. The interrelationships between these several aspects of scientific inquiry and the longterm objectives of the proposed research to enhance the knowledge base relevant to drug dependence potential and abuse liability is to be understood within the unifying conceptual framework of an environmental/biobehavioral model for integrating the multiple interacting levels of investigative effort focused upon drug-seeking and drug-taking as critical aspects of public health concern.