Introduction: The progenitor Wistar Kyoto (WKY) model, outbred from Wistar rats, demonstrates neurochemical and behav ioural profiles similar to symptom-presenting depressive patients and may be particularly suitable for teasing out interconnecting phenomena underlying depression and inflammation. Aims and Objectives: To investigate links between brain function and peripheral infection which has gained currency during the current pandemic, there is a need to find suitable models. Methods: Lipopolysaccharide (LPS) was administered to assay neurobehaviours, brain and liver enzyme activity. First, baseline indices of anxiety (elevated plus maze-EPM) and learned helplessness (forced swim test-FST) concerning Wistars was obtained. Results: WKYs demonstrated increased anxiety and inhibitory behaviours in the EPM while risk-taking was reduced. On habitu ation to the FST, WKY demonstrated reduced immobility, increased swimming and climbing behaviours. In the test, increased adaptive responses were observed. LPS induced a further increase in anxiety levels (EPM) with a concomitant decrease in exploratory behaviour in the novel activity box. Centrally, LPS reduced monoamine oxidase activity in the frontal cortex and hypothalamus while hypothalamic acetylcholinesterase activity was increased. Peripherally, LPS increased liver glutathione activity, with no effect on malondialdehyde at the dose tested. Conclusion: The WKY model could therefore prove a valuable model to test the __ampersandsignlsquo;double hit__ampersandsignrsquo; hypothesis in understanding the neuro-immune link in depression.