Animal Models Of Anxiety:a Behavioral 'Omics' Perspective

Objective:To establish a new animal model from a behavioral 'omics' perspective, so as to solve problems such as heterogeneity of animal models, repeated measures effects, and relationship between trait and state anxiety of animal models. Methods:First, animal models of anxiety were reviewed comprehensively, and two patterns were concluded from a behavioral "omics" perspective. Then, methodology such as behavioral pattern, test-retest reliability, about classical animal models of anxiety, such as open field test (OFT), elevated plus maze (EPM), elevated zero maze (EZM), light/dark box (LDB), free exploratory paradigm (FEP), was assessed by analysis. Finally, a modified triple integrated apparatus (mTIA), composed of OFT, modified EZM, and LDB, was behaviorally and pharmacologically validated. Results:Animal models of anxiety include "normal" "state" and "pathological" "trait" anxiety, which means that, 'normal' anxiety was referred to subjects experience anxiety at a particular moment in time and it is increased by the presence of anxiogenic stimulus, and 'pathological' anxiety was often referred to as 'trait' anxiety, considered to be an enduring feature of an individual. Total (Cross+Rear) for OFT, percentage of time in Open arms and entries into open and enclosed arms for EPM/EZM, Rear for LDB, percentage of time in novel compartments (Nrear%) for FEP, could be viewed reliable parameters. mTIA could be a new model for anxiety research, which displayed different patterns between male and female, and discriminated the pharmacological effects between diazepam (DZP) and alprazolam (APZ), that 4mg/kg DZP could increase percentage of time in open arms in mEZM and Cross in LDB, while APZ had no effect, two traditional Chinese formula Suanzaorentang (SZRT) and Jiaotaiwan (JTW), that 8mg/kg SZRT could increase percentage of time in open arms in mEZM, while 8 mg/kg JTW could increase percentage of time in central areas in OFT. Conclusion:Animal models of anxiety could be viewed from "normal" "state" and "pathological" "trait" perspective. More attention should be paid to sex, repeated measurement, and the reliable parameters, when OFT, EPM, EZM, LDB and FEP were used in battery. mTIA was sensitive to genetic/pharmacological influences on anxiety and locomotion and that, by providing quasi-simultaneous measures from three different apparatuses, it may represent an alternative to the use of test batteries, that may provide solution on such problems on animal models of anxiety.