THE USE OF A FULL SPECTRUM OF FEARFUL CHALLENGE INCREASES THE SENSITIVITY FOR ASSESSING RODENT FEAR AND ANXIETY

Abstract

Elevated plus maze (EPM) has been the golden standard for assessing rodent fear and anxiety but its sensitivity is unstable. Emotional dysfunction including disordered fear and anxiety has been a significant component of many psychiatric disorders, such as generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and Alzheimer's disease (AD). Therefore, it is necessary to study the reason why the EPM is sometimes insensitive, and to develop a more sensitive and stable method for assessing the fear and anxiety. We have compared an alternative method that we've developed recently, the elevated platform (EP) task, with the EPM in parallel for a couple of studies using different sets of mice. We also tested whether the variations of the shapes and transparency of the platform affect the sensitivity of the EP. This new EP task allows plotting the entire spectrum reactions of each animal in response to a continuous spectrum of fearful challenge. Such a design enables identification of the peak fear tolerance therefore permitting to use the peak values for comparisons rather than sometimes having to use sometimes non-peak values for comparisons as those for the close or open arms in the EPM. Moreover, having the full spectrum of the animal's responses also permits to standardize the animal's fearful tolerance and to assign each animal a fearful tolerance index (FTI) score that is inversely correlated with the anxiogenic tendency. The FTI score enables across cohorts/studies comparisons without significant variations among different cohorts/studies, if they were performed under the same conditions using the same standard protocol.