Orbitofrontal response to drug-related stimuli after heroin administration

The compulsion to seek and use heroin is frequently driven by stress and craving during drug-cue exposure. Although previous neuroimaging studies have indicated that craving is mediated by increased prefrontal cortex activity, it remains unknown how heroin administration modulates the prefrontal cortex response. This study examines the acute effects of heroin on brain function in heroin-maintained patients. Using a crossover, double-blind, placebo-controlled design, 27 heroin-maintained patients performed functional magnetic resonance imaging 20 minutes after the administration of heroin or placebo (saline) while drug-related and neutral stimuli were presented. Images were processed and analysed with statistical parametric mapping. Plasma concentrations of heroin and its main metabolites were assessed using high-performance liquid chromatography. Region of interest analyses showed a drug-related cue-associated blood-oxygen-level-dependent activation in the orbitofrontal cortex (OFC) in heroin-dependent patients during both treatment conditions (heroin and placebo). This activation of the OFC was significantly higher after heroin than after placebo administration. These findings may indicate the importance of OFC activity for impulse control and decision-making after regular heroin administration and may emphasize the benefit of the heroin-assisted treatment in heroin dependence. In the structural magnetic resonance imaging (MRI) analysis, heroin-dependent patients had less grey matter volume than healthy controls in the right medial frontal gyrus and right middle frontal gyrus (p < 0.01) (a). Drug-related cues were associated with significant BOLD (blood-oxygen-level-dependent) activation in the orbitofrontal cortex (OFC) after heroin and placebo administration (p < 0.01) (b). Analysis of treatment effects within heroin-dependent patients showed a significantly higher BOLD response in the right OFC after heroin than after placebo administration (p = 0.039) (c)