The impact of stress on fear memory retention. A meta-analysis of rodent fear conditioning studies

Pavlovian fear conditioning is a widely used behavioural task for studying fear memory in rodents. During conditioning, rodents learn to associate a conditioned stimulus (e.g., context or tone; contextual or auditory fear conditioning, CFC or AFC, respectively) with an aversive one (e.g., footshock), resulting in a conditioned fear response. Fear memory retention is assessed thorough freezing behaviour, a species-specific defensive reaction, observed during exposure to the conditioned stimulus alone. Fear memory is influenced by sex and stress, with stress exposure prior to conditioning potentially inducing maladaptive fear responses. This meta-analysis examines how pre-conditioning stress exposure modulates memory retention in rodents. Across N = 94 studies included, we analyzed freezing behaviour based on several factors: type of paradigm (CFC vs AFC), species (rat vs mouse), sex (male vs female), stress type (physical vs pharmacological vs psychological vs combination of two or more stressors type), stress duration (acute or chronic), stress timing (prenatal vs early postnatal vs adolescence vs adulthood). The results indicate that stress significantly enhances contextual conditioned freezing behaviour. Stress-induced effects in CFC models vary across species but are not sex-specific. Additionally, these effects are influenced by stress-related factors. These findings highlight the importance of considering multiple variables when studying stress and fear memory processes, offering valuable insights for improving clinical approaches to fear memory-related diseases (e.g., post-traumatic stress disorder).