The Affective Disorder Test: a new test to assess depression and anxiety-like behaviour in rats

Abstract

<p><b>Major depressive and anxiety disorders are debilitating psychiatric illnesses which are often a serious burden to the patients, their families and society as a whole. A major contributor to this burden is that a large number of patients do not respond to current therapeutics. As all treatments are established first in animal models, an imperative direction to advance treatment efficacy in humans is through progressing these models. This thesis aims to develop and validate a novel behavioural test (Affective Disorder Test: ADT) that simultaneously assesses depression and anxiety-like behaviours, as well as provides a more valid index of depression-like behaviour than previous tests, and allows repeated testing in the same animal.</b></p> <p>In order to develop a standardized protocol, the impact of food restriction on behaviour was examined. Subjects with ad libitum access to food, failed to exhibit sufficient responses in aspects of the test, supporting the incorporation of food restriction into the test protocol. The serotonin transporter knockout (SERT -/-) rat was employed as a model of depression and anxiety, and as hypothesised displayed corresponding behaviour in the test, indicating construct validity. Finally, the predictive validity of the test was corroborated as pharmacological treatment of anxiolytic and antidepressant drugs, diazepam (1 mg/kg) and ketamine (5 mg/kg), improved subjects behaviour on relevant areas of the test. The ADT is an innovate tool which has the ability to contribute to the scientific and general community by furthering our understanding of the aetiology of these disorders and enhancing pharmacological developments</p>

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

“…In addition to work mentioned in the thesis, our lab looked at behaviours related to anxiety and depression in the F1 offspring through the affective disorders test (ADT, Appendix E). The ADT is an adapted version of the successive alleys test (SAT) which provides a measure of anxiety and integrates a food reward which allows for the measurement of anticipatory pleasure (Blackburne, 2021). Analysis so far has shown no differences between the D1 and ND1 in terms of anxiety behaviours but there are sex x condition interactions in measured anticipatory behaviour with D1 females showing higher rearing, indicating more pronounced anticipation than ND1 females and D1 males showing lower rearing than ND1 males (Appendix E), indicating sexually dimorphic effects of PPAC on anticipatory (depression-related) behaviour.…”

“…Our lab looked at behaviours related to anxiety and depression in the F1 offspring through the affective disorders test (ADT). The ADT is an adapted version of the successive alleys test (SAT) with the integration of an anticipation box and food which provide measures of anticipation (Blackburne, 2021). Animals are maintained at 90% their free feeding weight for the duration of the experiment.…”