<p>Motherhood entails brain and behavioral changes associated with increased motivation for pups, ensuring their correct development and survival. Dopamine systems play a crucial role in motivated behaviors, although the exact neurobiological mechanisms underlying maternal behavior remain unknown. The tail of the ventral tegmental area (tVTA) or rostromedial tegmental nucleus (RMTg) is a control center of dopamine systems involved in avoidance and prediction error, among other brain processes. In the present study, we explored its possible contribution in maternal motivation in rats. To do so, we analyzed maternal behavior, as well as the expression of cFos in several brain regions (tVTA/RMTg, anterior–posterior VTA, shell-core ACb, mPFC, LHb, MePD, MPO) of virgin and dam rats in response to pups (Virgin-P, Dam-P) or to pup-predicting cues (absence of pups) (Virgin-NP, Dam-NP). Overall, our results reveal that maternal behavior was only displayed by dams, whereas virgins did not display maternal sensitization in our experimental conditions. Regarding the brain activity, we show that pup-predicting cues induce higher cFos in the tVTA/RMTg of pup-deprived dams compared to non-pup deprived dams and to virgin females, suggesting a role of the tVTA/RMTg in maternal reward prediction error. By contrast, pup exposure or deprivation elicit slight differences on the recruitment of other dopamine and social-related brain regions in our females. Finally, the correlation analysis of activity of brain regions mainly highlights positive correlations in pup-exposed females and scarce correlations in pup-deprived females. Overall, our results reveal a main role of the tVTA/RMTg in maternal reward prediction error.</p>