title: Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity.
abstract: Corticosteroid action in the brain is mediated by the mineralocorticoid (MR) and the glucocorticoid (GR) receptor. Disturbances in MR- and GR-mediated effects are thought to impair cognition, behavior, and endocrine control. To assess the function of the limbic MR in these processes, we inactivated the MR gene in the forebrain of the mouse using the Cre/loxP-recombination system. We screened the mice with a limbic MR deficiency in various learning and exploration tests. The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy. They exhibit a hyperreactivity toward a novel object but normal anxiety-like behavior. The behavioral changes are associated with abnormalities of the mossy fiber projection and an up-regulation of GR expression in the hippocampus. Adult mutant mice show normal corticosterone levels at circadian trough and peak. This genetic model provides important information about the consequences of a permanently altered balance between limbic MR and GR, with implications for stress-related neuroendocrine and neuropsychiatric diseases.
authors.affiliation: German Cancer Research Center, Division Molecular Biology of the Cell I, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Berger
authors.forename: David P
authors.initials: DP
authors.lastname: Wolfer
authors.forename: Oliver
authors.initials: O
authors.lastname: Selbach
authors.forename: Heike
authors.initials: H
authors.lastname: Alter
authors.forename: Gitta
authors.initials: G
authors.lastname: Erdmann
authors.forename: Holger M
authors.initials: HM
authors.lastname: Reichardt
authors.forename: Aisa N
authors.initials: AN
authors.lastname: Chepkova
authors.forename: Hans
authors.initials: H
authors.lastname: Welzl
authors.forename: Helmut L
authors.initials: HL
authors.lastname: Haas
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lipp
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000172:deficiency* / Q000235:genetics; D013239:Stereotyped Behavior / Q000502:physiology
chemical_list: D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003345:Corticosterone