Oxytocinergic and opioidergic action and interaction

In mammals, not only primary rewards (e.g. food, sex) but also social rewards (e.g. affiliative touch) are fundamental for well-being and health. While the neurochemistry of primary non-social rewards has been extensively studied both in animals and humans, research exploring the neurochemical basis of human social rewards is less conclusive. It has been recently documented that the combined exogenous manipulation of oxytocin and opioids leads to supralinear effects on social attention in non-human primates, suggesting that their interaction exceeds what could be expected from an additive effect. This groundbreaking finding opens new frontiers for research in humans. In this project, we aim at unravelling mechanisms of actions and interactions of oxytocin and opioids in human social behaviors. We will address three fundamental unresolved research questions: 1) How does social reward processing in humans depend on the combined action of the opioidergic and the oxytocinergic systems, above and beyond the action of each system alone? 2) What are the neural bases of such combined action? 3) Is the combined action of these two neurochemical systems specific for social vs. non-social rewards? In a monocentric, randomized, double-blind, placebo-controlled, four-period crossover study design, we will utilize an established translational social reward paradigm and will collect fMRI and behavioral data from 80 healthy female and male participants, undergoing administration of oxytocin, naltrexone (unspecific opioid antagonist), or a combination of both, compared to a placebo-control condition. Subjective (ratings) and objective (real effort, facial electromyography) responses to anticipation and consumption of social (human touch) and non-social (chocolate milk) rewards will be obtained at every trial. Special attention will be devoted to assess whether sex is a potential mediator of the observed effects. By means of a multi-level approach drawing upon methods and expertise from experimental psychology on the one side, and state-of-the-art neuroscience and neuropharmacology on the other, we expect our project to generate an unprecedentedly novel understanding of the neurobiology of social reward processing in humans, with future implications for treatments of reward processing anomalies in neuropsychiatric disorders.