title: Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats.
abstract: Reduced corticotropin-releasing factor (CRF) receptor activation in the postpartum period is essential for adequate maternal behavior. One of the factors contributing to this hypo-activity might be the CRF-binding protein (CRF-BP), which likely reduces the availability of free extracellular CRF/urocortin 1. Here, we investigated behavioral effects of acute CRF-BP inhibition using 5μg of CRF(6-33) administered either centrally or locally within different parts of the bed nucleus of the stria terminalis (BNST) in lactating rats. Additionally, we assessed CRF-BP expression in the BNST comparing virgin and lactating rats. Central CRF-BP inhibition increased maternal aggression during maternal defense but did not affect maternal care or anxiety-related behavior. CRF-BP inhibition in the medial-posterior BNST had no effect on maternal care under non-stress conditions but impaired the reinstatement of maternal care following stressor exposure. Furthermore, maternal aggression, particularly threat behavior, and anxiety-related behavior were elevated by CRF-BP inhibition in the medial-posterior BNST. In the anterior-dorsal BNST, CRF-BP inhibition increased only non-maternal behaviors following stress. Finally, CRF-BP expression was higher in the anterior compared to the posterior BNST but was not different between virgin and lactating rats in either region. Our study demonstrates a key role of the CRF-BP, particularly within the BNST, in modulating CRF's impact on maternal behavior. The CRF-BP is important for the reinstatement of maternal care after stress, for modulating threat behavior during an aggressive encounter and for maintaining a hypo-anxious state during lactation. Thus, the CRF-BP likely contributes to the postpartum-associated down-regulation of the CRF system in a brain region-dependent manner.
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany. Electronic address: stefanie.klampfl@ubc.ca.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Klampfl
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany. Electronic address: milena.schramm@ur.de.
authors.forename: Milena M
authors.initials: MM
authors.lastname: Schramm
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-2200, USA. Electronic address: schaferg@umich.edu.
authors.forename: Gwen S
authors.initials: GS
authors.lastname: Stinnett
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany. Electronic address: doris.bayerl@ur.de.
authors.forename: Doris S
authors.initials: DS
authors.lastname: Bayerl
authors.affiliation: Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109-2200, USA; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-2200, USA. Electronic address: aseashol@umich.edu.
authors.forename: Audrey F
authors.initials: AF
authors.lastname: Seasholtz
authors.affiliation: Department of Behavioural and Molecular Neurobiology, Institute of Zoology, University of Regensburg, Universitätsstr. 31, 93053 Regensburg, Germany. Electronic address: oliver.bosch@ur.de.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Bosch
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D007774:Lactation / Q000187:drug effects; D008425:Maternal Behavior / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C067133:corticotropin releasing factor-binding protein; D003346:Corticotropin-Releasing Hormone
keywords: Anxiety-related behavior; Bed nucleus of the stria terminalis; Corticotropin-releasing factor; Corticotropin-releasing factor-binding protein; Maternal aggression; Maternal care; Stress