Type: Master's thesisSupervisors: Siri Leknes, Marie Eikemo, Tom JohnstoneFinal grade: B (Norwegian grade system). See supplemental materials for grader evaluation document.The endogenous μ-opioid receptor (MOR) system in the brain is central to reward behaviors across species, and brain areas implicated in reward are dense with μ-opioid receptors. The MOR system has received the most interest through its involvement in pleasure mediation (‘liking’), but there is much evidence to suggest a role for the MOR system in motivated ‘wanting’ as well. Nevertheless, we still know very little about the mechanisms of MOR modulation in reward motivation in healthy humans. Further, it is unclear to what extent the animal research on MOR modulation of reward-processing in the brain can be extended to humans, as very few studies have explored this relationship directly in the human brain. We examined the effects of a low dose (10mg) of per oral morphine (a μ-opioid agonist) on reported food wanting, and of applying a cognitive regulation task to downregulate this wanting, in healthy human participants. We also measured neural activity as approximated by functional magnetic resonance imaging. The study was designed to minimize the risk of potential confound effects of the drug manipulation. In a within-subject, counterbalanced, placebo-controlled, double-blind design, 63 participants (31 male, mean age 27 ±5) were tested in a morphine and placebo session on two separate days. In line with our expectations, morphine did not significantly affect subjective mood or state, respiration- or heart rate, or motor coordination. Morphine also did not appear to alter global BOLD, measured by a simple visual control task. The food wanting task elicited significant activation in reward related regions compared to baseline, and cognitive regulation produced the expected decrease in food wanting, together with increased activity in ventral prefrontal regions. Activation in extrastriate occipital regions was observed across tasks. Preliminary analyses confirmed our hypothesis that MOR agonism would increase food wanting, but did not confirm our hypothesis of associated activity increase in the striatum and medial prefrontal areas. Instead, increased activity in regulation-related regions may be required for successful downregulation of wanting after morphine treatment. In summary, we have now validated the paradigm and task design of this study. Thus, a complete analysis of the drug effects of interest can be conducted and the results interpreted to draw meaningful conclusions regarding the effects of MOR stimulation with morphine on BOLD signals relating to ‘wanting’ for palatable food images.
Endogenous opioids in the nucleus accumbens promote approach to high-fat food in the absence of caloric need