title: Psychosocial stress is associated with in vivo dopamine release in human ventromedial prefrontal cortex: a positron emission tomography study using [¹⁸F]fallypride.
abstract: 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 100 min 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.
authors.affiliation: Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: Lataster
authors.forename: Dina
authors.initials: D
authors.lastname: Collip
authors.forename: Jenny
authors.initials: J
authors.lastname: Ceccarini
authors.forename: David
authors.initials: D
authors.lastname: Haas
authors.forename: Linda
authors.initials: L
authors.lastname: Booij
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.forename: Jens
authors.initials: J
authors.lastname: Pruessner
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.forename: Inez
authors.initials: I
authors.lastname: Myin-Germeys
mesh_terms: D000328:Adult; D001549:Benzamides; D001667:Binding, Competitive / Q000502:physiology; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007091:Image Processing, Computer-Assisted; D007553:Isotope Labeling; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D012931:Social Environment; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001549:Benzamides; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D004298:Dopamine; D006854:Hydrocortisone