Increased CRF-R1 transmission in the nucleus accumbens shell facilitates maternal neglect in lactating rats and mediates anxiety-like behaviour in a sex-specific manner

During the transition to motherhood, complex brain adaptations occur to ensure adequate maternal responses to offspring' needs accompanied by reduced anxiety. Among others, the corticotropin-releasing factor (CRF) and oxytocin (OXT) systems have emerged as crucial regulators of these essential postpartum adaptations. Here, we investigated their roles within the nucleus accumbens shell (NAcSh), a central region of the reward and maternal circuits, in maternal neglect of lactating rats. Furthermore, we assessed the contribution of the local CRF system to anxiety-like behaviour, comparing lactating female, virgin female and male rats to evaluate potential sex-differences. Increasing CRF receptor (CRF-R) 1 transmission via local CRF infusion in the NAcSh led to maternal neglect, reducing nursing and increasing self-directed behaviours. In turn, local CRF-R1 inhibition impaired maternal motivation. Intra-NAcSh Urocortin3 infusion did not promote maternal neglect but increased anxiety-like behaviour in lactating and virgin female rats, whereas CRF infusion had anxiogenic effects only in male rats. Crh-r1 mRNA expression was higher in male and lactating rats compared to virgin females; furthermore, male rats had increased Crh-bp mRNA expression compared to virgin female rats, only. Lastly, pharmacological manipulations of the OXT system did not affect maternal responses. In conclusion, finely balanced CRF-R1 signalling in the NAcSh is required for the proper expression of maternal behaviours. Dampened CRF-R2 signalling prevents the onset of anxiety-like behaviour in female rats, whereas CRF-R1 plays a more prominent role in males, highlighting complex sex-differences of the CRF system's regulation of anxiety within the NAcSh.