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Current therapeutics for major depressive disorder (MDD) have limited utility due to their extensive side effect profiles and limited efficacy. Additionally, there is an absence of extensive fast-acting antidepressant therapies. Serotonin is a neurotransmitter which is implicated in MDD and is responsible for various functions including mood regulation and stress responsiveness. Serotonin transporter knock-out (5-HTT KO) mice model the serotonergic dysfunction and behavioural endophenotypes intrinsic to a population of MDD patients. Iron is a metal which plays a role in various mechanisms relevant to MDD neuropathology and there is clinical evidence that brain iron levels may be elevated in MDD. Deferiprone is an iron chelator which has the capacity to rapidly cross the BBB. The aim of this thesis was to determine the behavioural effects of deferiprone on the 5-HTT KO mouse model of depression, relative to wild-type (WT) littermates. Furthermore, this thesis investigated brain regions involved in deferiprone treatment and its interaction with an acute stressor in the form of swim stress. Finally, deferiprone’s molecular mechanism of action was also investigated. The data presented indicates that deferiprone has acute antidepressant-like properties in both 5-HTT KO and WT mice. The antidepressant-like properties of deferiprone are more robust on the 5-HTT KO mouse model of depression, relative to WT littermate controls. Deferiprone also has pro-cognitive effects in the form of enhanced short-term spatial memory performance following chronic administration, irrespective of genotype. The acute antidepressant-like properties of deferiprone were attributed to regions of the lateral/basolateral amygdala, bed nucleus of the stria terminalis (BNST) and lateral septum. Graph theory-based analyses and hierarchical clustering was adopted to determine the effects of deferiprone and swim-stress exposure on the functional network of 5-HTT KO and WT mice. This revealed a divergenc