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Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tenden- cies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous l-opioid system is linked to long-term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in l-opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR-specific ligand ( 11 C)carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships-Revised scale. The avoidance dimension of attachment cor- related negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals' social relationships and psychosocial well-being. Hum

Physical exercise modulates food reward and helps control body weight. The endogenous µ‐opioid receptor (MOR) system is involved in rewarding aspects of both food and physical exercise, yet interaction between endogenous opioid release following exercise and anticipatory food reward remains unresolved. Here we tested whether exercise‐induced opioid release correlates with increased anticipatory reward processing in humans. We scanned 24 healthy lean men after rest and after a 1 h session of aerobic exercise with positron emission tomography (PET) using MOR‐selective radioligand [(11)C]carfentanil. After both PET scans, the subjects underwent a functional magnetic resonance imaging (fMRI) experiment where they viewed pictures of palatable versus nonpalatable foods to trigger anticipatory food reward responses. Exercise‐induced changes in MOR binding in key regions of reward circuit (amygdala, thalamus, ventral and dorsal striatum, and orbitofrontal and cingulate cortices) were used to predict the changes in anticipatory reward responses in fMRI. Exercise‐induced changes in MOR binding correlated negatively with the exercise‐induced changes in neural anticipatory food reward responses in orbitofrontal and cingulate cortices, insula, ventral striatum, amygdala, and thalamus: higher exercise‐induced opioid release predicted higher brain responses to palatable versus nonpalatable foods. We conclude that MOR activation following exercise may contribute to the considerable interindividual variation in food craving and consumption after exercise, which might promote compensatory eating and compromise weight control.

All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of “system level” connectivity in the brain is increasing rapidly, we lack “molecular level” information on brain networks and connectivity patterns. We introduce novel voxel‐based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ‐opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty‐one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ‐opioid receptor tracer. First, voxel‐by‐voxel “intracorrelations” (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel‐level opioid–serotonin intercorrelations (between neurotransmitters) were computed. Regional μ‐opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain–striatum–thalamus–amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker‐based rationale for targeted modulation of neurotransmitter networks. Hum Brain Mapp 35:1875–1884, 2014. © 2013 Wiley Periodicals, Inc.