Pup defence in lactating rats: The underlying neuropeptide signalling and their interactions in the nucleus accumbens shell

Maternal aggression is a core feature of rodent maternal behaviour to defend their offspring from potential threats and is modulated by corticotropin-releasing factor (CRF) and oxytocin (OXT) systems signalling. Here, we investigated the involvement of those neuropeptide systems in maternal aggression within the nucleus accumbens shell (NAcSh), a central region of the reward and maternal circuits. Infusion of CRF or Urocortin3 (CRF-receptor 2 agonist), as well as an OXT receptor antagonist, reduced maternal aggression, suggesting a role in pup defence. Furthermore, the effects of CRF infusion in the NAcSh continued beyond the maternal defence test (MDT), reducing nursing and increasing self-grooming. Corroborating the involvement of the stress system in maternal aggression, colocalization of CRF and cFos immunoreactive cells were increased in response to the MDT, regardless of pup presence. In addition, MDT exposure increased intra-NAc OXT release in lactating rats, which could be also triggered by local retrodialysis of CRF, but not Urocortin3. However, both ligands of the CRF system elicited dopamine (DA) release in different dynamics. Crh-r1 were predominantly expressed in the medial NAc on medium-sized spiny neurons (MSN), but also in the rostral part on GABAergic interneurons. Crh-r2 were mainly expressed in the rostral NAc and its expression on GABAergic interneurons increased towards the caudal pole. Lastly, we identified CRF-enriched projections to the NAcSh descending from the prefrontal cortex, the amygdala, and the paraventricular thalamus, among others.

In conclusion, intra-NAcSh dampened CRF system activity and enhanced OXT system transmission are indispensable for successful pup defence. Any perturbations like increased CRF system signalling might activate compensatory mechanisms to ensure adequate maternal behaviour.