title: Central administration of oxytocin receptor ligands affects cued fear extinction in rats and mice in a timepoint-dependent manner.
abstract: BACKGROUND
  Oxytocin (OXT) has been proposed as a potential therapeutic agent for post-traumatic stress disorder (PTSD).
  
  
  OBJECTIVE
  We aimed to verify whether pharmacological manipulation of the brain OXT system affects cued fear conditioning and fear extinction.
  
  
  METHODS
  Male rats and mice were intracerebroventricularly administered synthetic OXT (rats, 0.1 or 1.0 μg/5 μl; mice, 0.1 or 0.5 μg/2 μl) and/or an OXT receptor antagonist (OXTR-A; rats, 0.75 μg/5 μl) either prior to fear conditioning or extinction training.
  
  
  RESULTS
  Preconditioning administration of OXT did not affect fear conditioning in rats, but decreased fear expression and facilitated fear extinction. In contrast, preconditioning blockade of OXT neurotransmission by OXTR-A did not affect fear conditioning or fear expression, but impaired fear extinction. When administered before extinction training, OXT impaired fear extinction in both rats and mice, indicating that the effects of OXT on fear extinction are conserved across species. This impairment was OXTR-mediated, as the inhibitory effect of OXT on fear extinction was abolished by prior treatment with OXTR-A. The impaired fear extinction was not a result of reduced locomotion in rats, whereas an apparent decrease in fear expression and facilitation of fear extinction with the higher OXT dose in mice was the result of behavioral hyperactivity.
  
  
  CONCLUSIONS
  These results suggest that increasing OXT neurotransmission during traumatic events is likely to prevent the formation of aversive memories. In contrast, OXT treatment before fear extinction training, which would be the comparable timepoint for psychotherapy in PTSD patients, rather delays fear extinction and, therefore, caution is needed before recommending OXT for the treatment of PTSD.
authors.affiliation: Department of Behavioral and Molecular Neurobiology, Faculty of Biology and Preclinical Medicine, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
authors.forename: Iulia
authors.initials: I
authors.lastname: Toth
authors.forename: Inga D
authors.initials: ID
authors.lastname: Neumann
authors.forename: David A
authors.initials: DA
authors.lastname: Slattery
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological; D003463:Cues; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects* / Q000523:psychology; D007276:Injections, Intraventricular; D008024:Ligands; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D010121:Oxytocin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000378:metabolism*; D012153:Retention, Psychology / Q000187:drug effects; D013045:Species Specificity; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D013997:Time Factors
chemical_list: D008024:Ligands; C576074:OXTR protein, mouse; D018045:Receptors, Oxytocin; D010121:Oxytocin