A critical inquiry into marble-burying as a preclinical screening paradigm of relevance for anxiety and obsessive-compulsive disorder: Mapping the way forward.

Rodent marble-burying behavior in the marble-burying test (MBT) is employed as a model or measure to study anxiety- and compulsive-like behaviors or anxiolytic and anticompulsive drug action. However, the test responds variably to a range of pharmacological interventions, and little consensus exists regarding specific methodologies for its execution. Regardless, the test is widely applied to investigate the effects of pharmacological, genetic, and behavioral manipulations on purported behaviors related to the said neuropsychiatric constructs. Therefore, in the present review we attempt to expound the collective translational significance of the MBT. We do this by (1) reviewing burying behavior as a natural behavioral phenotype, (2) highlighting key aspects of anxiety and obsessive-compulsive disorder from a translational perspective, (3) reviewing the history and proof of concept of the MBT, (4) critically appraising potential methodological confounds in execution of the MBT, and (5) dissecting responses of the MBT to various pharmacological interventions. We conclude by underlining that the collective translational value of the MBT will be strengthened by contextually valid experimental designs and objective reporting of data.