Sanson Alice, Demarchi Luisa, Rocaboy Emma, Bosch Oliver J
Department of Behavioural and Molecular Neurobiology, Regensburg Center of Neuroscience, University of Regensburg, Regensburg, Germany.
Neuropharmacology. 2025 Mar 1;265:110256. doi: 10.1016/j.neuropharm.2024.110256. Epub 2024 Dec 6.
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.
在向母亲角色转变的过程中，大脑会发生复杂的适应性变化，以确保母亲能充分应对后代的需求，并减少焦虑。其中，促肾上腺皮质激素释放因子（CRF）和催产素（OXT）系统已成为这些产后重要适应性变化的关键调节因子。在此，我们研究了它们在伏隔核壳（NAcSh）中的作用，NAcSh是奖赏和母性行为回路的核心区域，涉及哺乳期大鼠的母性忽视行为。此外，我们评估了局部CRF系统对焦虑样行为的影响，比较了哺乳期雌性、未生育雌性和雄性大鼠，以评估潜在的性别差异。通过在NAcSh局部注入CRF增加CRF受体（CRF-R）1的传递会导致母性忽视，减少哺育行为并增加自我导向行为。反之，局部抑制CRF-R1会损害母性行为动机。在NAcSh内注入尿皮质素3不会促进母性忽视，但会增加哺乳期和未生育雌性大鼠的焦虑样行为，而注入CRF仅在雄性大鼠中产生致焦虑作用。与未生育雌性大鼠相比，雄性和哺乳期大鼠的Crh-r1 mRNA表达更高；此外，仅与未生育雌性大鼠相比，雄性大鼠的Crh-bp mRNA表达增加。最后，对OXT系统的药理学操作并未影响母性行为反应。总之，NAcSh中精细平衡的CRF-R1信号传导是母性行为正常表达所必需的。减弱的CRF-R2信号传导可防止雌性大鼠出现焦虑样行为，而CRF-R1在雄性大鼠中起更突出的作用，突出了CRF系统在NAcSh内调节焦虑方面的复杂性别差异。
