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

Abstract

Rodent studies suggest that dopamine signaling at D_2/3 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 D_2/3 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 D_2/3 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.