title: Oxytocin differentially modulates pavlovian cue and context fear acquisition.
abstract: Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety.
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Cavalli
authors.affiliation: Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Ruttorf
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Mario Rosero
authors.initials: MR
authors.lastname: Pahi
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zidda
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.affiliation: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Nees
mesh_terms: D001921:Brain / Q000187:drug effects; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000187:drug effects*; D003463:Cues; D004311:Double-Blind Method; D017352:Echo-Planar Imaging; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects*; D005260:Female; D005712:Galvanic Skin Response / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D010121:Oxytocin
keywords: context; cue; fear conditioning; magnetic resonance imaging; oxytocin