Opioid antagonism modulates wanting-related frontostriatal connectivity

Abstract

Theoretical accounts distinguish between 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 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. Reducing 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. In contrast, reducing dopaminergic neurotransmission with amisulpride revealed no robust effects on behavior or neural activity. Our findings thus provide insights into how opioid receptors mediate neural connectivity related to specifically motivational, not hedonic, aspects of rewards.

Trial registration: ClinicalTrials.gov NCT02557984.

Keywords: dopamine; human; liking; neuroscience; opioid; reward; striatum; wanting.

Conflict of interest statement

AS, SW, BQ, PT No competing interests declared, TK Reviewing editor, eLife

© 2021, Soutschek et al.

Figures

Figure 1.. Task procedure and behavioral results.

(A) Participants rated in the MRI scanner how much they wanted or liked objects before (pre-test) or after (post-test) they won or lost these items in a game between the scanning sessions. (B) On each trial, a cue indicated whether a wanting or liking rating was required, followed by the presentation of the current object (here: a pick-up sticks game). Participants had to rate how much they wanted or liked the presented object within 3.5 s, then the next trial started after a variable inter-trial interval (mean = 3 s). (C) Liking ratings were significantly reduced for objects that were lost relative to won in the gamble, while wanting ratings did not significantly differ between lost versus won items. (D) The opioid antagonist naltrexone significantly reduced wanting ratings relative to placebo, while liking ratings were unaffected by naltrexone or the dopamine antagonist amisulpride. For illustration purposes, participant-specific mean wanting/liking ratings are plotted on a scale from 0 to 10, while the statistical analyses are conducted on the participant- and item-specific wanting and liking ratings. Error bars indicate standard error of the mean, black dots represent individual data points. *p < 0.05, ***p < 0.001.

Figure 2.. Neural correlates of (A) wanting and (B) liking independently of behavioral relevance.

Wanting correlated with activation in dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), and posterior cingulate cortex (PCC) (whole-brain FWE-corrected). Liking correlated with activation in dorsal PCC (whole-brain FWE-corrected) and orbitofrontal cortex (small-volume FWE-corrected). (C) Wanting ratings significantly correlated with activation in the striatum during wanting judgements (small-volume FWE-corrected). Images are thresholded at p < 0.001 uncorrected.

Figure 3.. Effects of Judgement type and drug on parametric striatal connectivity.

(A) On wanting trials (collapsed across drug groups), dorsolateral prefrontal cortex (DLPFC)-striatum connectivity was enhanced for wanting relative to liking aspects of rewards (image thresholded at p < 0.001 uncorrected). (B) Wanting-related DLPFC-striatum coupling was significantly stronger under naltrexone compared with placebo (image thresholded at p < 0.001 uncorrected). (C, D) Extracted parameter estimates for DLPFC (as defined by the significant cluster in general linear model 1 [GLM-1]), separately for wanting and liking judgements. (C) If wanting judgements were behaviorally relevant, naltrexone increased wanting relative to liking-related DLPFC-striatum connectivity. (D) No significant drug effects on DLPFC-striatum connectivity were observed on liking trials. Error bars indicate standard error of the mean, black dots represent individual data points. *p < 0.05.