Influence of State and/or Trait Anxieties of Wistar Rats in an Anxiety Paradigm

Abstract

Systematic individual differences between male Wistar rats can be detected in paradigms such as the elevated plus maze (EPM), which is a widely used behavioral paradigm that measures fear-motivated avoidance behavior. It has been extensively used to assess anxiety profiles with face, construct and predictive validities. During a typical EPM test, animals actively avoid the open arms in favour of the closed arms. We investigated whether individuals carry inherent trait anxiety profiles and whether perturbations of different intensities influence anxiety measures. Inherent anxiety levels and coping strategies following stress have become critical determinants in pre-disposition to other neuropsychiatric disorders and affect biomedical interventions in individuals. One group of rats was screened on EPM and in the activity box. Another set of rats were randomly divided into groups and subjected to perturbations of acute and sub-chronic isolation or restraint and tested in the EPM. Based on open-arm time in the EPM, low or high anxiety profiles were identified with significant differences in all measures. Perturbations of different intensities induced differential anxiety measures as expressed in the EPM. Anxiety levels were significantly reduced in sub-chronic restrained subjects, while isolation did not show marked difference. Anxiety profiles become evident from broad sample sizes and could constitute a critical limiting factor in personalized treatments. Stress-induced anxiety disorders could implicate comorbidity to other neuropsychiatric disorders in individuals. Coping strategies come to the fore in repeated sub-chronic perturbations indicating adaptive responses to the stressor, while acute perturbation enhances expression of anxiety behaviors.

Keywords: Behavior; Elevated plus maze; Population; Restraint; Stress.

Fig. 1

a Scatter plot of open arm time on the EPM. Open-arm times of all animals were plotted serially. The dividing line indicates the median split used to classify the rats into 2 groups based on open-arm time into HA and LA groups. b Anxiety index of LA group was significantly lower than HA group. Anxiety index was calculated as: 1 - ((open-arm time/total time) + (open-arm entries/total entries))/2. The read-out of the anxiety index correlates with the open-arm times. The whiskers of the box plot represent minimum to maximum. *** p < 0.001.

Fig. 2

Pre-test perturbation-induced open-arm times on EPM: control vs. acute isolation/restraint and sub-chronic isolation/restraint. Iso-2 = Isolation for 2 h, Res-2 = restraint for 2 h, Iso-2 × 5 = isolation of 2 h on 5 consecutive days, Res-2 × 5 = restraint of 2 h on 5 consecutive days. * p < 0.05; ** p < 0.01; *** p < 0.001.