Gene × Disease Interaction on Orbitofrontal Gray Matter in Cocaine Addiction

Abstract

Drug addiction is a chronic disease associated with deficits in brain dopamine¹ (DA) and brain function in regions underlying the impaired response inhibition and salience attribution syndrome (see Goldstein and Volkow² for review). These regions encompass the reward and the inhibitory circuitry that contain DA-receptive neurons, where ventral prefrontal regions such as the orbitofrontal cortex (OFC) have received much emphasis.^2,3 Multiple neuroimaging studies in the past decade demonstrated a reliable pattern of functional deficits during cognitive/emotional challenges that involve reward contingencies (salience attribution) and inhibitory control (response inhibition) in cocaine use disorders (CUD).^4,5 For example, positron emission tomography and functional magnetic resonance (MR) imaging studies have demonstrated that DA-related functional deficits in the OFC may underlie disproportionate salience attribution to cocaine and compulsive drug intake.^3,5-7