Kufahl, P. R., Li, Z., Risinger, R. C., Rainey, C. J., Wu, G. H., Bloom, A. S., et al. (2005). Neural responses to acute cocaine administration in the human brain detected by fMRI. Neuroimage, 28(4), 904-914.

An improved functional MRI (fMRI) method for the reduction of susceptibility artifacts has been utilized to measure blood oxygen level-dependent (BOLD) responses to acute cocaine administration in the human brain of cocaine users. Intravenous administration of cocaine (20 mg/70 kg) activated mesolimbic and mesocortical dopaminergic projection regions and showed temporal positive or negative BOLD responses. These results obtained from human cocaine users supported the involvement of the dopaminergic pathway in cocaine addiction from animal models. In addition, the cocaine administration also induced activations in the hierarchical brain networks in the anterior prefrontal cortex (aPFC) of the Brodmann area 10 (BA10) and orbitofrontal cortex (OFC). It is suggested that the dopaminergic pathways and the hierarchical brain networks may participate in mediating cocaine reward processes, associative learning, motivation, and memory in cocaine addiction in the human brain. (c) 2005 Elsevier Inc. All rights reserved.

[not in handout, see intranet]
Risinger, R. C., Salmeron, B. J., Ross, T. J., Amen, S. L., Sanfilipo, M., Hoffmann, R. G., et al. (2005). Neural correlates of high and craving during cocaine self-administration using BOLD fMRI. Neuroimage, 26(4), 1097-1108.

Modern theories of drug dependence hold the hedonic effects of drug-taking central to understanding the motivation for compulsive drug use. Previous neuroimaging studies have begun to identify brain regions associated with acute drug effects after passive delivery. In this study, a more naturalistic model of cocaine self-administration (SA) was employed in order to identify those sites associated with drug-induced high and craving as measures of reward and motivation. Non-treatment seeking cocaine-dependent subjects chose both when and how often i.v. cocaine administration occurred within a medically supervised SA procedure. Both functional magnetic resonance imaging (fMRI) data and real-time behavioral ratings were acquired during the 1-h SA period. Drug-induced HIGH was found to correlate negatively with activity, in limbic, paralimbic, and mesocortical regions including the nucleus accumbens (NAc), inferior frontal/orbitofrontal gyrus (OFC), and anterior cingulate (AC), while CRAVING correlated positively with activity in these regions. This study provides the first evidence in humans that changes in subjective state surrounding cocaine self-administration reflect neural activity of the endogenous reward system. (c) 2005 Elsevier Inc. All rights reserved.