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

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.

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