Background: In mothers, offspring cues are associated with a powerful reinforcing value that motivates maternal care. Animalstudies show that this is mediated by dopamine release into the nucleus accumbens, a core component of thebrain’s reward system located in the ventral striatum (VStr). The VStr is also known to respond to infant signalsin human mothers. However, it is unknown whether pregnancy modifies the anatomy or functionality of thisstructure, and whether such modifications underlie its strong reactivity to offspring cues. Therefore, we analyzedstructural and functional neuroimaging data from a unique pre-conception prospective cohort study involvingfirst-time mothers investigated before and after their pregnancy as well as nulliparous control women scanned atsimilar time intervals. First, we delineated the anatomy of the VStr in each subject’s neuroanatomical space andexamined whether there are volumetric changes in this structure across sessions. Then, we tested if these changescould predict the mothers’brain responses to visual stimuli of their infants. We found decreases in the right VStrand a trend for left VStr reductions in the women who were pregnant between sessions compared to the womenwho were not. Furthermore, VStr volume reductions across pregnancy were associated with infant-related VStrresponses in the postpartum period, with stronger volume decreases predicting stronger functional activation tooffspring cues. Thesefindings provide thefirst indications that the transition to motherhood renders anatomicaladaptations in the VStr that promote the strong responsiveness of a mother’s reward circuit to cues of her infant.