Post-traumatic stress disorder (PTSD) is a debilitating mental health condition for which current treatments have long-term efficacy in 50% of patients. There is a clear need for better understanding of the mechanisms underlying PTSD and the development of new treatment approaches. Analogue trauma procedures in animals, such as the stress-enhanced fear learning (SEFL) procedure, can be used to produce behavioural and neurobiological changes that have validity in modelling PTSD.However, by necessity the modelling of PTSD in animals requires causing potential pain and suffering to the animals. Consistent with the '3Rs' (reduction, refinement, replacement) of animal research, this study aimed to determine whether the SEFL procedure can be refined to reduce potential animal pain and suffering while retaining the same behavioural and neurobiological changes. Here we showed that PTSD-relevant changes could be produced in both behaviour and the brain of rats that were group-rather than single-housed and that received lower magnitude electric shocks in the 'trauma analogue' session. We also varied the number of shock exposures in the trauma analogue session, finding SEFL-susceptible and SEFL-resilient populations at all levels of shock exposure, but with greater levels of shock increasing the proportion of rats showing the SEFL-susceptible phenotype. These data demonstrate that the SEFL procedure can be used as an animal analogue of PTSD with reduced potential pain and suffering to the animals, and that variations in the procedure could be used to generate specific proportions of SEFL-susceptible and SEFL-resilient animals in future studies.
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