Neurobiological substrates of cue-elicited craving and anhedonia in recently abstinent opioid-dependent males

Abstract

AimDrug-related stimuli may induce craving in addicted patients, prompting drug-seeking behaviour. In addition, studies have shown addicted patients to be less sensitive to pleasant, but non-drug-related, stimuli; a condition generally referred to as anhedonia. The neural correlates of cue-induced craving and anhedonia in opioid-dependent patients are, however, not well understood. We studied brain activation patterns following visual presentation of neutral, pleasant and heroin-related cues. MethodsDetoxified opioid-dependent males (n=12) and healthy male control subjects (n=17) underwent functional magnetic resonance imaging (fMRI) while subjects viewed neutral, pleasant and heroin-related images. In addition, subjective cue-elicited craving (OCDUS and DDQ) and anhedonia (SHAPS) were measured. ResultsOpioid-dependent subjects, but not control subjects, showed significant increases in activation in hippocampal region and subcortical limbic structures in response to heroin-related stimuli with a significant group×stimulus interaction effect for the subthalamic nucleus (STN). Control subjects, but not opioid-dependent subjects, showed significant increases in activation of anterior frontal areas and basal ganglia while viewing pleasant images with a significant group×stimulus interaction effect for bilateral anterior prefrontal cortex. Regression analyses showed a positive association between cue-elicited craving and ventral tegmental area (VTA) activation in response to heroin-related stimuli in heroin-dependent patients. In addition, a negative correlation was found between self-reported anhedonia and medial prefrontal regions in both groups. ConclusionsOur findings suggest that the VTA is prominently involved in cue-induced opioid craving for heroin stimuli, in addition to mesolimbic and mesocortical pathways as identified in previous research. The present study also provides further evidence for the involvement of the STN in reward processing. Finally, our data support the presence of reduced brain activation in heroin-dependent patients in response to pleasant (non-drug-related) stimuli.