Altered maternal profiles in corticotropin-releasing factor receptor 1 deficient mice.
BACKGROUND
During lactation, the CNS is less responsive to the anxiogenic neuropeptide, corticotropin-releasing factor (CRF). Further, central injections of CRF inhibit maternal aggression and some maternal behaviors, suggesting decreased CRF neurotransmission during lactation supports maternal behaviors. In this study, we examined the maternal profile of mice missing the CRF receptor 1 (CRFR1). Offspring of knockout (CRFR1-/-) mice were heterozygote to offset possible deleterious effects of low maternal glucocorticoids on pup survival and all mice contained a mixed 50:50 inbred/outbred background to improve overall maternal profiles and fecundity.


RESULTS
Relative to littermate wild-type (WT) controls, CRFR1-/- mice exhibited significant deficits in total time nursing, including high arched-back, on each test day. Consistent with decreased nursing, pups of CRFR1-deficient dams weighed significantly less than WT offspring. Licking and grooming of pups was significantly higher in WT mice on postpartum Day 2 and when both test days were averaged, but not on Day 3. Time off nest was higher for CRFR1-/- mice on Day 2, but not on Day 3 or when test days were averaged. Licking and grooming of pups did not differ on Day 2 when this measure was examined as a proportion of time on nest. CRFR1-/- mice showed significantly higher nest building on Day 3 and when tests were averaged. Mean pup number was almost identical between groups and no pup mortality occurred. Maternal aggression was consistently lower in CRFR1-/- mice and in some measures these differences approached, but did not reach significance. Because of high variance, general aggression results are viewed as preliminary. In terms of sites of attacks on intruders, CRFR1-/- mice exhibited significantly fewer attacks to the belly of the intruder on Day 5 and when tests were averaged. Performance on the elevated plus maze was similar between genotypes. Egr-1 expression differences in medial preoptic nucleus and c-Fos expression differences in bed nucleus of stria terminalis between genotype suggest possible sites where loss of gene alters behavioral output.


CONCLUSIONS
Taken together, the results suggest that the presence of an intact CRFR1 receptor supports some aspects of nurturing behavior.
Gammie
Stephen C
SC
Department of Zoology, University of Wisconsin, Madison, Wisconsin 53706, USA. scgammie@wisc.edu
Bethea
Emily D
ED
Stevenson
Sharon A
SA
D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling / Q000523:psychology; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005260:Female; D006120:Grooming / Q000502:physiology; D007774:Lactation / Q000235:genetics / Q000378:metabolism; D008297:Male; D008425:Maternal Behavior / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D011301:Preoptic Area / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D012686:Septal Nuclei / Q000033:anatomy & histology / Q000378:metabolism / Q000503:physiopathology; D000099052:CRF Receptor, Type 1
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone