BRAIN IMAGING OF COCAINE EFFECTS

The diversity of cocaine's effects in humans indicates that the drug acts on multiple specific brain pathways. As a step toward sorting out cocaine's multiple actions on the brain, the investigators hope to define the brain mechanisms mediating cocaine's subjective effects, particularly euphoria. Until 1998 the investigators used positron-emission tomography (PET) with radio-labeled water to measure regional cerebral blood flow (rCBF) following intravenous cocaine administration. In 1998 the study was amended to allow the use of complementary brain imaging modality, magnetic resonance imaging (MRS). MRSI is a functional imaging procedure which displays local metabolic changes in the brain following an intervention (here, administration of cocaine), uses no ionizing radiation, and is free of some of the limitations and potential artifacts of rCBF mapping with PET. Subjects will be chronic intravenous cocaine abusers, not seeking treatment, of both genders, between the ages of 21 and 45. They will be admitted to the GCRC for eight days. The specific aims of the study are (1) to use MRSI to define the time course of the brain's metabolic response after acute administration of a single dose of cocaine), and correlate cocaine-related changes in MRS with concurrent measures of subjective experience, cardiovascular effects, and circulating cocaine levels; and (2) to compare the brain regions where MRS changes correlate with subjective experience, cardiovascular effects or circulating cocaine levels with data from the previous PET study, which used a parallel experimental protocol.