Major depressive disorder usually presents as a complex mixture of emotional, cognitive and somatic symptoms. Current treatments include both pharmacological and psychological approaches. However, a significant proportion of patients fail to respond and the disease can develop into a very severe and debilitating, treatment resistant disorder. Despite the availability of drug treatments for more than 60 years and extensive clinical and pre-clinical research, the underlying biology of depression remain elusive. Our work focuses on studies to try to understand how cognitive affective processes (affective biases) contribute to the disease and the actions of antidepressant drugs. This seminar will describe our work developing translational rat models of affective biases. I will discuss how we have used pharmacological and psychosocial manipulations of affective state to test the validity of the approach and how these studies have led to some novel hypotheses about the role of affective biases in the cause and perpetuation of the condition. This includes a novel hypotheses about the mechanisms of action and rate of onset of antidepressant drugs. The final part of the talk will discuss some new data relating to reward and deficits in reward learning which are distinct from more conventional measures of anhedonia but strongly linked to a depression-like phenotype.