Changes in maternal motivation across reproductive states in mice: A role for prolactin receptor activation on GABA neurons.

The survival of newborn offspring in mammals is dependent on sustained maternal care. Mammalian mothers are highly motivated to interact with and care for offspring, however, it is unclear how hormonal signals act on neural circuitry to promote maternal motivation during the transition to motherhood. In this study we aimed to establish methods that enable us to evaluate change in maternal motivation across the reproductive life cycle in female mice. Using two behavioural testing paradigms; a novel T-maze retrieval test and a barrier climbing test, we found that pup retrieval behaviour was low in virgin and pregnant mice compared to lactating females, indicating that maternal motivation arises around the time of parturition. Furthermore, in reproductively experienced females, maternal motivation declined over time after weaning of pups. As we have previously shown that lactogenic action mediated through the prolactin receptor (Prlr) in the medial preoptic area (MPOA) is essential for the expression of maternal behaviour, we aimed to investigate the role of lactogenic hormones in promoting pup-related motivational behaviours. With GABAergic neurons expressing Prlr in multiple brain regions important for maternal behaviour, we conditionally deleted Prlr from GABA neurons. Compared to control females, lactating GABA neuron-specific Prlr knockout mice showed slower and incomplete pup retrieval behaviour in the T-maze test. Testing of anxiety behaviour on an elevated plus maze indicated that these mice did not have increased anxiety levels, suggesting that lactogenic action on GABA neurons is necessary for the full expression of motivational aspects of maternal behaviour during lactation.