Neural activity related to drug craving in cocaine addiction

Background: Crack cocaine dependence and addiction is typically associated with frequent and intense drug wanting or craving triggered by internal or environmental cues associated with past drug use. Methods: Water O 15 positron emission tomography (PET) studies were used to localize alterations in synaptic activity related to cue-induced drug crav ing in 8 crack cocaine-dependent African American men. In a novel approach, script-guided imagery of autobiographical memories were used as individual ized cues to internally generate a cocaine craving state and 2 control (ie, anger and neutral episodic memory recall) states during PET image acquisit ion. Results: The mental imagery of personalized drug use and anger-related scri pts was associated with self-ratings of robust drug craving or anger, and c omparable alterations in heart rate. Compared with the neutral imagery cont rol condition, imagery-induced drug craving was associated with bilateral ( right hemisphere amygdala activation greater than left) activation of the a mygdala, the left insula and anterior cingulate gyrus, and the right subcal losal gyrus and nucleus accumbens area. Compared with tile anger control co ndition, internally generated drug craving was associated with bilateral ac tivation of the insula and subcallosal cortex, left hippocampus, and anteri or cingulate cortex and brainstem. A brain-wide pixel-by-pixel search indic ated significant positive and negative correlations between imagery-induced cocaine craving and regional cerebral blood flow (rCBF) in distributed sit es. Conclusions: The collected findings suggest the craving-related activation of a network of limbic, paralimbic, and striatal brain regions, including s tructures involved in stimulus-reward association (amygdala), incentive mot ivation (subcallosal gyrus/nucleus accumbens), and anticipation (anterior c ingulate cortex).