Despite extensive efforts, the precise site and the underlying mechanisms of morphine action have not been ascertained. To date, experiments indicate that specific central nervous system sites involving separate functions (but perhaps with close interrelationships) are responsible for the acute, chronic and withdrawal phenomena resulting from morphine action. The basal ganglia, midbrain nuclei, thalamic nuclei, the hypothalamus and limbic structures are often considered the most likely sites of morphine action and each group of nuclei participates differently in the morphine mode of action. It is the objective of this research proposal to examine systematically in two different preparations the neurophysiological properties underlying the mechanisms of acute narcotic effects (for example, analgesia), in relation to certain chronic actions (tolerance and dependent phenomena), and in relation to the withdrawal symptoms. These will be accomplished by studying systematically and simultaneously several functional systems within the brain which will provide the comparative aspects of structure-function relations contributing to the different actions of morphine. The proposed study is unique in that it focuses on the elementary processes underlying the organization of complex neuronal activities of which the sensorimotor and somatosensory subcortical regulatory mechanisms are comprised. Single unit activity will be recorded in sites proposed to be involved in the acute effects produced by morphine, chronic effects (dependent and tolerance) and sites proposed to be involved in the withdrawal phenomena. Also, evoked activity and "spontaneous" discharges will be studied systematically in freely behaving (unanesthetized) preparations as well as in acute experiments using the current "state of the art" techniques of unit recording and iontophoretic application of the drugs in both acute and dependent models. Putting together these experimental findings will provide information that will supply the knowledge for understanding complicated phenomena such as analgesia, tolerance, physical dependence and withdrawal. Therefore, the proposed study is a novel approach to understanding the physiological properties of narcotic action on the brain.