Changes in cognition and emotion are a common concomitant of psychiatric and neuropsychiatric disorders. In prior work from this project we had demonstrated a close link between motivational state and memory performance of depressed patients, and had examined the effects of naloxone as a strategy to examine this linkage further. In normals, a dose of 2 mg/kg or higher of naloxone increased depression and anxiety ratings and induced decrements in memory performance. This year, we have tested the effects of 2 mg/kg of naloxone in depressed subjects, together with a second group of normals. Depressives manifested a more marked and subjectively more intense response to naloxone compared to normals. We have also examined the effects of naloxone in Alzheimer's patients. Preliminary data suggest that Alzheimer patients show behavioral and cognitive changes at lower naloxone doses than those effective in young normals. Two other drug strategies being actively investigated include the use of monoamine oxidase inhibitors and cholinergic antagonists in our efforts to continue to explore the links between cognition and emotion and its neuropharmacology.