A series of studies are proposed to investigate the biological basis of individual differences in responses to drugs of abuse in humans. Although it is widely recognized that individuals differ in their responses to drugs, little is known about the biological mechanisms underlying these differences. The proposed studies will focus on the central nervous system effects of hormones and their potential interactions with drugs of abuse. The first series of studies will assess the effects of ovarian hormones and their interactions with psychoactive drugs in women. These studies are designed to investigate the direct mood-altering and behavioral effects of estrogen and progesterone, and the interactions of these hormones with psychoactive drugs. The second series of studies is designed to assess the effects of glucocorticoids alone and on responses to d-amphetamine. These studies are based on evidence from laboratory animals indicating that stress hormones, in particular glucocorticoids, enhance the reinforcing effects of stimulant drugs. The proposed studies will investigate the direct mood-altering and behavioral effects of exogenously administered hydrocortisone in healthy human volunteers, and explore the interactions between cortisol levels and responses to drugs. In the final proposed study we will investigate the biological basis of the stimulant-like effects experienced by some individuals after ingestion of ethanol. Together, the studies will extend our understanding of the source of individual differences in responses to abused drugs, and they will further our knowledge of the interactions of drugs and hormones in the brain.
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