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Preliminary studies have demonstrated individual differences in metabolic and subjective responses to psychoactive drugs in humans. A strong relationship was found between mood changes induced by ethanol and changes in cerebral metabolism in the temporal and parietal cortices of the brain. The studies proposed here would extend these findings to other abused drugs and to other subject populations.

The relationship between the subjective and cognitive effects of drugs and their effects on regional cerebral metabolism of glucose (rCMglu) will be studied in normal volunteers using positron emission tomography (PET) with 18fluoro-2-deoxy-d-glucose (2FDG) as the tracer. Three studies will be conducted. The first and second studies will examine the effects of diazepam and amphetamine on rCMglu and mood. The third study will extend previous findings with ethanol to additional groups: males who are light social drinkers, males who are moderate social drinkers, and females who are light social drinkers. In all studies, subjects will first participate in a behavioral preference procedure, in which individual responses to the mood-altering effects and reinforcing effects of each drug will be measured in a naturalistic situation. Subjects will then participate in the PET sessions, one with placebo and two with different doses of the drug. Mood effects of the drugs will also be monitored during PET sessions. A PET-MRI image correlation and subtraction procedure will be utilized to identify regions of interest on the PET images.

Knowledge gained about the correspondence between brain activity and subjective responses to abused drugs may improve our understanding of why certain drugs are abused and why certain individuals are at risk for abusing them.
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