Maternal profiling of corticotropin-releasing factor receptor 2 deficient mice in association with restraint stress

Abstract

Mice deficient in corticotropin releasing factor receptor 2 (CRF2) (C57BL/6J:129Sv background) exhibit impaired maternal defense (protection of offspring) and are more reactive to stressors than wild-type mice. To further understand CRF2's role in maternal behavior, we crossed the knockout mice with a line bred for high maternal defense that also has elevated maternal care relative to inbred lines. Maternal care was normal in knockout mice (relative to wild-type). Maternal defense was impaired as previously observed. Exposure to a mild stressor (15 min restraint) did not trigger deficits in maternal defense in either genotype as determined by a two-way repeated measures ANOVA analysis. However, when examining difference scores between unrestrained and restrained conditions, knockout mice exhibited significant decreases in maternal defense with stress, suggesting knockouts are more susceptible to a mild stressor's effects. To gain possible insights into brain activity differences between WT and KO mice, we examined c-Fos expression in association with stress. Unrestrained KO mice exhibited significantly lower c-Fos levels relative to unrestrained WT mice in 9 regions, including lateral septum and periaqueductal gray. For WT mice, restraint stress triggered c-Fos activity increases in 3 regions while for KO mice, restraint stress triggered c-Fos increases in 16 regions. Taken together, our results suggest both altered behavioral and c-Fos responses to stress in lactating CRF2 KO mice.

Neurotensin inversely modulates maternal aggression

“…Also, in rats pup removal for 2.5 h does not alter baseline corticosterone or adrenocorticotropic hormone (ACTH) levels, but does dampen ACTH increases in response to a male intruder (Deschamps et al, 2003). We do not think that removal of pups just before testing had a strong stress effect on mothers that altered aggression, but even if it did, mild stressors do not impair aggression (Gammie and Stevenson, 2006, D’Anna et al, 2009) and pup removal was consistent for all testing. The maternal aggression test began by introducing a male intruder for 5 min.…”

CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

“…Moreover, we found that CRF-R2 activation decreased the occurrence of total nursing implying that the CRF-R2 agonist-treated dams nurse less promptly after the infusion, which was later reversed. In accordance, CRF-R2 are generally considered to aid stress recovery upon activation ( Bale et al, 2002 , Bale and Vale, 2004 , Reul and Holsboer, 2002 ) and genetic deletion of CRF-R2 impairs maternal aggression in lactating mice ( D’Anna et al, 2008 ). In contrast, CRF-R2 activation in the mpBNST of lactating rats is detrimental to maternal behavior ( Klampfl et al, 2014 ).…”

Reduced brain corticotropin‐releasing factor receptor activation is required for adequate maternal care and maternal aggression in lactating rats

“…Maternal motivation of lactating HAB, LAB, and NAB dams was assessed in the pup retrieval test (van Leengoed et al ., ; Neumann et al ., ). Manipulation of the CRF system did not alter retrieval behaviour, which is in line with studies revealing that mice deficient for one of the two CRF‐Rs (Gammie et al ., ; D'Anna et al ., ) or for the CRF‐binding protein (Gammie et al ., ) do not show differences in retrieval behaviour compared with wild type mice. Hence, maternal motivation seems to be unaffected by the central CRF system.…”