Multiparity alters expression of corticotropin releasing factor receptor 1 and co-expression with oxytocin neurons in mice

Corticotropin releasing factor (CRF) signaling through its primary receptor (CRFR1) regulates various stress-related behaviors and neuroendocrine responses. CRFR1 is also a key regulator of stress-related behavior changes during the postpartum period in rodents. Previous studies indicate dynamic changes in CRFR1 in various brain regions during the first postpartum period including an emergence of CRFR1 expression in hypothalamic oxytocin neurons. We sought to determine how these changes in CRFR1 and CRFR1/oxytocin co-expression might be altered with repeated breeding cycles and whether these neural adaptations coincide with changes in maternal behaviors that are reported to occur in rodent dams with greater maternal experience. CRFR1-GFP reporter mice were bred to produce 1 (primiparous) or 3 (multiparous) litters and were assessed for pup retrieval in unstressed and stressed (male intruder) conditions. Brains of nulliparous, primiparous, and multiparous mice were collected to assess CRFR1-GFP and co-expression of CRFR1 with oxytocin. No statistically significant changes in pup retrieval were found between primiparous and multiparous mice although both groups showed a greater latency to hover over pups following male intruder exposure. However, multiparity increased oxytocin/CRFR1 co-expression relative to primiparous and nulliparous mice in the paraventricular hypothalamus (PVN) and supraoptic nucleus (SON). Multiparous mice also showed elevated CRFR1-GFP in the PVN and SON relative to primiparous mice. In the medial preoptic area and anteroventral periventricular nucleus, primiparous, but not multiparous mice differed in CRFR1-GFP levels relative to nulliparous mice. Together, these findings indicate dynamic changes in CRFR1 with multiparity that may contribute to stress-related behavior changes.