Oxytocin receptors in the nucleus accumbens shell are necessary for the onset of maternal behavior in post-parturient mice

Oxytocin (Oxt) signaling via its receptor, the Oxt receptor (Oxtr), is important to the onset of mammalian maternal care. Specifically, evidence suggests that Oxt signaling around the time of parturition underlies the critical shift in how pups are perceived, i.e. from aversive stimuli to rewarding stimuli. Previous work from our lab has found that both Oxtr knockout (-/-) mice and forebrain-specific Oxtr knockout (FB/FB) are more likely than controls to abandon their first litters. Based on these data, we hypothesized that this observed pup abandonment phenotype was due to a failure of the brain to "switch" to a more maternal state. In order to identify where in the brain Oxt signaling contributes to the onset of maternal care we performed three experiments. In Experiment 1, virgin Oxtr FB/FB females were assessed for genotypic differences in maternal behavior and c-Fos expression following maternal sensitization was quantified. In Experiment 2, c-Fos expression was quantified in Oxtr -/- and Oxtr FB/FB females following parturition. In Experiment 3, based on our findings from Experiment 2, the Oxtr in the nucleus accumbens shell (NAcc) was genetically deleted in female Oxtr floxed mice (Oxtr Flox/Flox) mice using a Cre recombinase expressing adeno-associated virus. In Experiment 1, sensitized virgin Oxtr FB/FB females had significantly lower retrieval latencies on the first day of testing and reduced c-Fos expression in the dorsal lateral septum compared to controls. In Experiment 2, increased c-Fos expression was observed in the NAcc shell of both Oxtr -/- and Oxtr FB/FB dams as compared to controls. In Experiment 3, virally mediated knockout of the Oxtr in the NAcc shell completely disrupted the onset of maternal care. Thus, by genetically deleting Oxtr expression in the NAcc the pup abandonment phenotype previously observed in Oxtr -/- and Oxtr FB/FB dams was recreated. Taken together, these data suggest that in post-parturient mice, Oxtr expression in the NAcc shell is critical to the onset of maternal behavior.