title: Hypoactivation of CRF receptors, predominantly type 2, in the medial-posterior BNST is vital for adequate maternal behavior in lactating rats.
abstract: Maternal behavior ensures the proper development of the offspring. In lactating mammals, maternal behavior is impaired by stress, the physiological consequence of central corticotropin-releasing factor receptor (CRF-R) activation. However, which CRF-R subtype in which specific brain area(s) mediates this effect is unknown. Here we confirmed that an intracerebroventricularly injected nonselective CRF-R antagonist enhances, whereas an agonist impairs, maternal care. The agonist also prolonged the stress-induced decrease in nursing, reduced maternal aggression and increased anxiety-related behavior. Focusing on the bed nucleus of the stria terminalis (BNST), CRF-R1 and CRF-R2 mRNA expression did not differ in virgin versus lactating rats. However, CRF-R2 mRNA was more abundant in the posterior than in the medial BNST. Pharmacological manipulations within the medial-posterior BNST showed that both CRF-R1 and CRF-R2 agonists reduced arched back nursing (ABN) rapidly and after a delay, respectively. After stress, both antagonists prevented the stress-induced decrease in nursing, with the CRF-R2 antagonist actually increasing ABN. During the maternal defense test, maternal aggression was abolished by the CRF-R2, but not the CRF-R1, agonist. Anxiety-related behavior was increased by the CRF-R1 agonist and reduced by both antagonists. Both antagonists were also effective in virgin females but not in males, revealing a sexual dimorphism in the regulation of anxiety within the medial-posterior BNST. In conclusion, the detrimental effects of increased CRF-R activation on maternal behavior are mediated via CRF-R2 and, to a lesser extent, via CRF-R1 in the medial-posterior BNST in lactating rats. Moreover, both CRF-R1 and CRF-R2 regulate anxiety in females independently of their reproductive status.
authors.affiliation: Department of Behavioural and Molecular Neurobiology, University of Regensburg, 93053 Regensburg, Germany, and.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Klampfl
authors.affiliation: Division of Neurobiology, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, United Kingdom.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Brunton
authors.affiliation: Department of Behavioural and Molecular Neurobiology, University of Regensburg, 93053 Regensburg, Germany, and.
authors.forename: Doris S
authors.initials: DS
authors.lastname: Bayerl
authors.affiliation: Department of Behavioural and Molecular Neurobiology, University of Regensburg, 93053 Regensburg, Germany, and oliver.bosch@ur.de.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Bosch
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D007774:Lactation / Q000187:drug effects; D008297:Male; D008425:Maternal Behavior / Q000523:psychology*; D018782:Maze Learning / Q000187:drug effects; D009042:Motivation / Q000502:physiology; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C482465:phenylalanyl corticotropin-releasing factor; D003346:Corticotropin-Releasing Hormone