ACUTE EFFECTS OF COCAINE ON HUMAN BRAIN ACTIVITY AND EMOTION

We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while sub jects rated scales for rush, high, low, and craving. Cocaine induced f ocal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC ), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, p arahippocampal gyrus, cingulate, lateral prefrontal and temporal corti ces, parietal cortex, striate/extrastriate cortices, Ventral tegmentum , and pens and produced signal decreases in amygdala, temporal pole, a nd medial frontal cortex. Saline produced few positive or negative act ivations, which were localized to lateral prefrontal cortex and tempor o-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might ref lect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These in cluded the ventral tegmentum, pens, basal forebrain, caudate, cingulat e, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correla ted with craving than with rush ratings; such regions included the NAc /SCC, right parahippocampal gyrus, and some regions of lateral prefron tal cortex. Sustained negative signal change was noted in the amygdala , which correlated with craving ratings. Our data demonstrate the abil ity of fMRI to map dynamic patterns of brain activation following coca ine infusion in cocaine-dependent subjects and provide evidence of dyn amically changing brain networks associated with cocaine-induced eupho ria and cocaine-induced craving.