Through an integrated program of basic and clinical studies, we shall continue to examine the effects of opiates and amphetamines on catecholamine metabolism, and to explore the role of catecholamines in the reinforcing properties of these drugs and in the pathophysiology of opiate and amphetamine addition. The basic studies include: 1) studies of the effects of acute and chronic administration of morphine and d- or l-amphetamine on norepinephrine turnover, as determined by levels of 3-methoxy-4-hydroxyphenylglycol sulfate--MHPG-SO4, in rat brain regions; 2) studies to determine whether the morphine-induced increase in MHPG sulfate levels in rat brain can be conditioned; 3) studies of the effects of morphine and amphetamines on thresholds of intracranial reinforcement and locomotor activity. Through these neuropharmacological studies we hope to be able to explore possible relationships among the neurochemical, physiological and behavioral effects of opiates and amphetamines. In clinical studies, we shall continue to examine the effects of heroin and amphetamines on urinary catecholamines and metabolites in an attempt to confirm and extend previous findings. In particular, we shall further explore the possible relationship between changes in catecholamine metabolism and various physiological and behavioral variables including drug seeking behavior.