Psychosocial stress is associated with in vivo dopamine release in human ventromedial prefrontal cortex: A positron emission tomography study using [18F]fallypride

• Published in: NeuroImage (Orlando, Fla.) Vol. 58; no. 4; pp. 1081 - 1089
• Main Authors: Lataster, Johan, Collip, Dina, Ceccarini, Jenny, Haas, David, Booij, Linda, van Os, Jim, Pruessner, Jens, Van Laere, Koen, Myin-Germeys, Inez
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.10.2011; Elsevier Limited
• Subjects: Adult; Age; Benzamides; Binding, Competitive - physiology; Brain; Cortisol; Data Interpretation, Statistical; Dopamine; Dopamine - metabolism; Fallypride; Female; Humans; Hydrocortisone - blood; Image Processing, Computer-Assisted; Isotope Labeling; Kinetics; Male; Middle Aged; Positron-Emission Tomography; Prefrontal; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - metabolism; Pyrrolidines; Radiopharmaceuticals; Social Environment; Stress; Stress, Psychological - diagnostic imaging; Stress, Psychological - metabolism; Studies; Teenagers; Young Adult; Cortisol; Dopamine; Prefrontal; Fallypride; Stress
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2011.07.030

Rodent studies suggest that prefrontal dopamine neurotransmission plays an important role in the neural processing of psychosocial stress. Human studies investigating stress-induced changes in dopamine levels, however, have focused solely on striatal dopamine transmission. The aim of this study was to investigate in vivo dopamine release in the human prefrontal cortex in response to a psychosocial stress challenge, using the highly selective dopamine D2/3 PET radioligand [18F]fallypride in healthy subjects. Twelve healthy subjects (age (y): 39.8; SD=15.8) underwent a single dynamic Positron Emission Tomography (PET) scanning session after intravenous administration of 185.2 (SD=10.2) MBq [18F]fallypride. Psychosocial stress was initiated at 100min postinjection. PET data were analyzed using the linearized simplified reference region model (LSRRM), which accounts for time-dependent changes in [18F]fallypride displacement. Voxel-based statistical maps, representing specific D2/3 binding changes, were computed to localize areas with increased ligand displacement after task initiation, reflecting dopamine release. The psychosocial stress challenge induced detectable amounts of dopamine release throughout the prefrontal cortex, with dopaminergic activity in bilateral ventromedial prefrontal cortex being associated with subjectively rated experiences of psychosocial stress. The novel finding that a mild psychosocial stress in humans induces increased levels of endogenous dopamine in the PFC indicates that the dynamics of the dopamine-related stress response cannot be interpreted by focusing on mesolimbic brain regions alone. ► Measuring in vivo dopamine release in human PFC under stressful conditions. ► Psychosocial stress challenge induces detectable amounts of dopamine release in PFC. ► Dopamine release in vmPFC correlates positively with perceived level of stress. ► Important role for (vm)PFC dopamine in the human stress response.