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.