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If maternal separation and exposure to novelty were combined, then after the third such daily exposure, the sensitivity to the stressor was further enhanced. Meanwhile, basal corticosterone and ACTH levels were persistently suppressed 16 h after pups were reunited with their mothers. To explain the HPA axis desensitization after repeated separation, we found that circulating ghrelin levels increased and glucose levels decreased after all periods of maternal separation, ruling out a role of altered metabolism. Glucocorticoid feedback was not involved either because a glucocorticoid receptor antagonist amplified the corticosterone response after the first but became ineffective after the third separation. In contrast, a mineralocorticoid receptor antagonist decreased and increased corticosterone levels after the first and third period of separation, respectively. In conclusion, the newborn\u2019s HPA axis readily desensitizes to repeated daily maternal separation, but continues to respond to novelty in a manner influenced by a central mineralocorticoid receptor- rather than glucocorticoid receptor-mediated mechanism.<\/jats:p>","DOI":"10.1210\/en.2008-0238","type":"journal-article","created":{"date-parts":[[2008,7,18]],"date-time":"2008-07-18T01:10:18Z","timestamp":1216343418000},"page":"6366-6377","source":"Crossref","is-referenced-by-count":54,"title":["Hypothalamic-Pituitary-Adrenal Axis Activity of Newborn Mice Rapidly Desensitizes to Repeated Maternal Absence but Becomes Highly Responsive to Novelty"],"prefix":"10.1210","volume":"149","author":[{"given":"L.","family":"Enthoven","sequence":"first","affiliation":[{"name":"Division of Medical Pharmacology, Leiden\/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, 2300 RA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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