Opioidergic regulation of human affiliative behavior - Evidence from positron emission tomography studies

Humans display a remarkable pattern of affiliative behavior. We talk, laugh, play games, and celebrate various events, such as birthdays. Our social networks are also much larger than those of our evolutionary closest cousins, nonhuman primates. Social life is so important for humans that social problems, such as isolation and loneliness, are detrimental to our mental and somatic health. Sociality is indeed one of the basic human needs, similarly as food, water, and safety. Despite the fundamental role of sociality to humans, the neurobiological mechanisms influencing human affiliative behavior are still poorly understood. Animal models of social behavior suggest that endogenous opioid system–a neurotransmitter system modulating pain and pleasure in all mammals–regulates also affiliative behavior. Proposedly, motivation for social interaction partly arises from decreased opioidergic activity in the brain, and various forms of social behavior increase opioidergic processing. This increase results in pleasant affective states and facilitates inter-personal bonding between the interacting individuals. While the results from animal studies are mostly consistent with this model, it is still unknown whether and how the opioid system regulates affiliative behavior of humans. The aim of this Thesis was to characterize the role of the opioid system in human affiliative behavior using neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). The Thesis focuses on individual differences in self-reports of approach–avoidance behavior and affective responses measured with fMRI. The Thesis also tested if laughing induces release of endogenous opioids. [11C]carfentanil, a selective µ-opioid receptor (MOR) agonist tracer, was used to quantify cerebral MOR availability in all four studies. The first study showed that cerebral MOR availability is positively associated with approach motivation. This finding is in line with data from animal studies, suggesting that baseline opioidergic activity influences how actively humans seek reward. The second study showed that laughing with friends induces endogenous opioid release, consistent with the hypothesis that laughing facilitates interpersonal bonding in humans via opioidergic mechanisms. The third and fourth studies showed that individuals with high MOR availability, particularly in rostral anterior cingulate cortex and insular cortex, have blunted hemodynamic responses to painful and otherwise arousing movie scenes. These findings are consistent with the opioid system's role in regulation of pain and anxiety, suggesting that inter-individual differences in MOR availability may explain why some humans often find themselves highly aroused, while others may be perfectly calm in the same situations. In sum, results of the Thesis support the involvement of opioids in transmitting not only signals related to pain and pleasure but also to sociality in humans.