Citation

Clark JW, Drummond SPA, Hoyer D, Jacobson L. Br. J. Pharmacol. 2019; ePub(ePub): ePub.

Affiliation

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 30 Royal Parade, Parkville, Victoria, 3052, Australia.

Copyright

(Copyright © 2019, John Wiley and Sons)

DOI

10.1111/bph.14600

PMID

30710446

Abstract

BACKGROUND AND PURPOSE: Women are overrepresented in Posttraumatic stress disorder (PTSD); a mental disorder characterised by ineffective inhibition of fear. The use of male animals dominates pre-clinical studies, which may contribute to a lack of understanding as to why this disparity exists. Thus, the current study explores sex differences in three mouse models of fear inhibition. EXPERIMENTAL APPROACH: All experiments tested male and female C57Bl/6J mice. Experiment One employed two fear conditioning protocols, in which tones were paired with footshocks of differing intensity (moderate or intense). Fear recall and extinction were tested subsequently. In Experiment Two, safety learning was investigated. Tones were explicitly unpaired with footshocks during safety conditioning. Recall of safety learning was tested 24-hours later. Experiment Three assessed a model of fear-safety discrimination. Cued stimuli were paired or never paired with footshocks during fear and safety conditioning, respectively. Discrimination between stimuli was assessed 24-hours later. KEY RESULTS: In fear extinction, males, compared to females, responded with greater fear in sessions most proximal to conditioning, but subsequently showed a more rapid fear extinction over time. Sex differences were not observed during safety learning. During fear-safety discrimination, both males and females discriminated between stimuli, however, males revealed a greater level of freezing to stimuli.

CONCLUSION AND IMPLICATIONS: The current study provides evidence that sex differences influence fear, but not safety-based behaviour in C57Bl/6J mice. These findings indicate processing of fear, but not safety, may play a greater role in sex differences observed for PSTD.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

Sex; context; cue; discrimination; extinction; fear; posttraumatic stress disorder; recall; safety