Opioid antagonism reduces wanting by strengthening frontostriatal connectivity

Abstract

Goal-directed behavior depends on both motivational ("wanting") and hedonic ("liking") dimensions of rewards. Previous animal and human research linked wanting and liking to anatomically and neurochemically distinct brain mechanisms, but it remains unknown as to how the different brain regions and neurotransmitter systems interact in processing distinct reward dimensions. Here, we assessed how pharmacological manipulations of opioid and dopamine receptor activation modulate the neural processing of wanting and liking in humans in a randomized, placebo-controlled, double-blind clinical trial. Blocking opioid receptor activation with naltrexone selectively reduced wanting of rewards, which on a neural level was reflected by stronger coupling between dorsolateral prefrontal cortex and the striatum under naltrexone compared with placebo. Our findings thus provide insights into how opioid receptors mediate frontostriatal gating of specifically motivational, not hedonic, aspects of rewards.