Abstract
The μ-opioid receptor system is central to reward and pain relief across species. In rodents, injection of opioids into striatum amplifies liking responses to and/or motivation for rewards. In humans, opioid agonists can induce euphoria, whereas antagonists reduce food reward. Brain regions implicated in reward processing such as the mesolimbic reward system are rich in μ-opioid receptors. We investigated the role of the μ-opioid receptor system in human reward processing using systemic manipulation with a μ-opioid receptor agonist (morphine). In a functional magnetic resonance imaging (fMRI) pilot study we developed test procedures to measure reward related brain activity to anticipation and delivery of rewards, and to minimise potential confounds related to the pharmacological manipulation. We predicted activity in in the ventral striatum during anticipation and delivery of reward in a modified monetary incentive delay (MID) task, and that this activation would be higher in the morphine condition compared to placebo. In a within-subjects, counter-balanced, placebo-controlled, double-blind design, 11 healthy volunteers (4 females, mean age 26 ± 3 years) were tested on a battery of reward tasks on two separate days. In line with previous research, our version of the MID task yielded significant activation in the ventral striatum during anticipation and delivery of rewards, compared to baseline. We also observed an indication of higher activation in the morphine condition compared to placebo in the left ventral putamen during reward delivery. Control measures (subjective effects, motor coordination, physiological measures, and a visual fMRI paradigm) revealed minimal confounding effects of drug manipulation on task results. These results validate our test procedures and are in line with the hypothesis that systemic stimulation of the μ-opioid receptor system modulates activity in the ventral striatum during reward processing. The methods developed in this thesis will be used in the future study investigating the role of the μ-opioid receptor system for reward and motivation in the healthy human brain.