Type 2 diabetes, characterized by insulin resistance, has been linked to mood disorders, but the underlying mechanisms are not well understood. Kleinridders et al. now show that mice lacking the insulin receptor in the brain display increased depression- and anxiety-like behaviours. Decreased dopamine release in the striatum was also observed in these mice, and anti-depressant drugs that increase dopamine levels attenuated depression-like behaviours. These findings suggest that mood disorders in diabetes are caused by insulin resistance in the CNS and involve disruption of dopaminergic pathways.