We have extended our previous work investigating the neural correlates of cue-induced cocaine craving through the use of positron emission tomography with greater spatial resolution ( Ͻ 4.6 mm), an evocative script, and a pixelby-pixel analysis. Craving and cerebral glucose metabolism were measured after presentation of cocaine-related or neutral cues to 11 cocaine abusers. Cocaine cues elicited a higher degree of craving than has been previously reported and resulted in left hemispheric activation of lateral amygdala, lateral orbitofrontal cortex, and rhinal cortex and right hemispheric activation of dorsolateral prefrontal cortex and cerebellum. The intensity of activation in these areas (except cerebellum), as well as left insula, was also correlated with craving. Deactivation occurred in left ventral pole and left medial prefrontal cortex. The results suggest that induction of drug craving involves a neural network that assigns incentive motivational value to environmental stimuli through the coactivation of brain regions that process information about memories and emotions. Positron emission tomography (PET), Cerebral glucose metabolismCocaine craving is a complex phenomenon that contributes to relapse after abstinence from drug use. Selfreports of drug craving can be evoked reliably in a laboratory setting by presenting cocaine-related stimuli to cocaine abusers (Childress et al. 1993;Ehrman et al. 1992). Our research group has previously demonstrated that exposing cocaine abusers to a videotape depicting persons engaged in cocaine use and paraphernalia related to cocaine use induced craving and increases in regional cerebral metabolic rates for glucose in many cortical areas, including the dorsolateral prefrontal cortex, the medial orbitofrontal cortex (OFC), and the temporal lobe (Grant et al. 1996). Cue-induced craving was also correlated with an increase in rCMRglc (regional cerebral metabolic rate for glucose) in the medial temporal lobe (amygdala), dorsolateral prefrontal cortex, and cerebellum. These regions have been implicated in several forms of memory (Molchan et al. 1994;Tulving et al. 1999) NO . 3 Neural Systoms of Cue-Induced Cocaine Craving 377 brain imaging studies that investigated cocaine craving using positron emission tomography (PET) (Childress et al. 1999;Kilts et al. 2001;Volkow et al. 1999;) and functional magnetic resonance imaging (fMRI) (Breiter et al. 1997;Garavan et al. 2000;Maas et al. 1998;Wexler et al. 2001) have supported our original evidence that a number of cortical and subcortical brain regions involved in emotional memory are activated during craving.In this study, we sought to extend our previous observations using a positron emission tomograph with greater spatial resolution ( Ͻ 4.5 vs. 8.6 mm, within-plane full width at half maximum [FWHM]), a script that described in detail the physiological and psychological sensations associated with being high on cocaine, and a pixel-by-pixel analysis (rather than a region-of-interest analysis). The accumulation of published...

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [11 C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

The orbitofrontal cortex (OFC) plays a central role in human behavior. Anatomically connected with association areas of all sensory modalities, limbic structures, prefrontal cortical regions that mediate executive function and subcortical nuclei, this brain region can serve to integrate the physical and emotional attributes of a stimulusobject and establish a motivational value based on estimation of potential reward. To the extent that addictive disorders reflect a dysregulation of the ability to evaluate potential reward against harm from drug self-administration, it would be anticipated that substance abuse disorder might reflect dysfunction of the OFC. With the application of brain imaging techniques to the study of human substance abuse, evidence has been obtained that activity in the OFC and its connections plays a role in several components of the maladaptive behavior of substance abuse, including expectancy, craving and impaired decision making.