Reward motivation in humans and its relationship to dopamine D 2/3 receptor availability: A pilot study with dual [ 11 C]-raclopride and [ 11 C]-(+)-PHNO imaging

J Psychopharmacol. 2018 Mar;32(3):357-366. doi: 10.1177/0269881118756059. Epub 2018 Feb 14.

Abstract

Rodent studies suggest that dopamine signaling at D2/3 receptors in the ventral striatum is critical for reward motivation. Whether this is also true in humans is unclear. Positron emission tomography studies in healthy humans have generally not observed a relationship between D2/3 receptor availability in the ventral striatum and motivation. We developed the "mounting-effort for reward task" to assess high motivational demand for (a) gaining money (CS+), (b) losing money or avoiding electric shock (CS-), and (c) non-reward (Neutral). Receipt was contingent on participants making sufficient button responses relative to a "reward-threshold" determined by prior motor performance. This reward-threshold was dynamically increased if surpassed, making the task increasingly more difficult on every trial. The mounting-effort for reward task was preliminarily validated in 29 healthy volunteers (mean age: 25.83±3.58; 15 female). In this sample, %CS+ and %CS- significantly correlated with different dimensions of self-reported apathy. In a sub-sample of eight healthy volunteers (mean age: 25.75±1.91; four female), the mounting-effort for reward task demonstrated good test-retest reliability (%variance: 0.20-2.61%). Seven healthy male volunteers (mean age: 31.14±5.43) completed the mounting-effort for reward task and provided both [11C]-raclopride and [11C]-(+)-PHNO PET scans to assess D2/3 receptor availability. %CS+ and %CS- were positively correlated with [11C]-raclopride binding in the dorsal striatum. %CS+, %Cs-, and %Neutral were positively correlated with [11C]-(+)-PHNO binding in the globus pallidus. Thus, increased expression of D2 receptors in the dorsal striatum, and D3 receptors in the globus pallidus, may be related to motivation for rewards. Larger positron emission tomography studies are required to formally validate the mounting-effort for reward task and replicate our pilot findings.

Keywords: [11C]-(+)-PHNO; [11C]-raclopride; dopamine; motivation; positron emission tomography.

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Carbon Isotopes / metabolism*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism
  • Female
  • Globus Pallidus / drug effects
  • Globus Pallidus / metabolism
  • Healthy Volunteers
  • Humans
  • Male
  • Motivation / drug effects*
  • Pilot Projects
  • Positron-Emission Tomography / methods
  • Raclopride / therapeutic use*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Reproducibility of Results
  • Reward

Substances

  • Antipsychotic Agents
  • Carbon Isotopes
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Raclopride
  • Dopamine