Impaired motivation to seek reward (anhedonia) has been proposed to be caused by changes in the top-down (cortical) control of subcortical reward pathways. Here, Ferenczi et al. combine optogenetics with functional MRI and testing of reward-related behaviours to assess this idea. They show that, in rats, increased medial prefrontal cortex activity reduces the striatal blood oxygen level-dependent signal in response to midbrain dopamine neuron stimulation, alters functional interactions between cortical and limbic brain regions, and suppresses reward-related behaviours.