A meta-analysis of the effect of protein synthesis inhibitors on rodent fear conditioning

Systematic reviews and meta-analyses have been increasingly recognized for their potential value in pre-clinical research, but their multiple applications have not been extensively explored in behavioral neuroscience. In this work, we studied protein synthesis inhibition, a classic intervention used to disrupt fear learning, reconsolidation, and extinction in rodents, to explore how meta-analyses can identify potential moderators of its effect. We initially performed separate meta-analyses for different injection sites (systemic, hippocampus, amygdala, and cerebral ventricles) and target sessions (training, reconsolidation and extinction) to evaluate the effect of the intervention in various scenarios. Heterogeneity was further investigated by uni- and multivariable meta-regression using models aggregating various sites, with article or research group as additional levels. We detected robust effects of protein synthesis inhibitors on training and reconsolidation, but not on extinction, possibly due to the lower number of studies on the latter. Our analyses identified some well-established moderators, such as injection timing for training interventions and reexposure duration for reactivation interventions. However, other factors proposed as boundary conditions for reconsolidation, such as training strength and memory age, were not associated with effect size across the literature. Additionally, our findings suggest some underexplored associations, such as a larger susceptibility of cued fear conditioning to reconsolidation when compared to the contextual version of the task. While our results point to the value of meta-analyses in consolidating findings from the literature, we believe that associations suggested by data synthesis should ideally be verified by well-powered, rigorous confirmatory experiments.