Opioid antagonism modulates wanting-related frontostriatal connectivity

Elife. 2021 Nov 11:10:e71077. doi: 10.7554/eLife.71077.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amisulpride / pharmacology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / drug effects
  • Dopamine Antagonists / pharmacology
  • Dorsolateral Prefrontal Cortex / diagnostic imaging
  • Dorsolateral Prefrontal Cortex / drug effects
  • Double-Blind Method
  • Female
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Motivation / drug effects*
  • Naltrexone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Reward

Substances

  • Dopamine Antagonists
  • Narcotic Antagonists
  • Naltrexone
  • Amisulpride

Associated data

  • ClinicalTrials.gov/NCT02557984

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.