title: Puberty marks major changes in the hippocampal and cortical c-Fos activation pattern induced by NMDA receptor antagonists.
abstract: Non-selective and subunit (GluN2B)-specific N-methyl-d-aspartate receptor (NMDAR) antagonists represent promising alternative antidepressant drugs with fast onset of the therapeutic action. The neuronal activation pattern induced by NMDAR antagonists is well characterized by c-Fos expression analysis only in the adult rodent brain. In contrast, there is little information available regarding their effects during postnatal development. Here we performed a systematic c-Fos brain mapping of the non-selective NMDAR antagonist MK-801 and the GluN2B-specific antagonist Ro 25-6981 from postnatal day 16 (P16) to P40. We found significant regional differences with gender-specificity in the activation pattern compared to the adult. Surprisingly, in the hippocampus, MK-801 triggered at pre-pubertal stages (especially at P24) very strong c-Fos expression, followed by low levels after P30, the approximate time point of puberty onset in mice. The cortical distribution of MK-801-triggered c-Fos expression before puberty differed also substantially from the adult brain, showing high levels only in deep cortical layers at pre-pubertal stages. In comparison, the cortical activation induced by Ro 25-6981 diminished from high pre-pubertal levels and was in comparison with that triggered by MK-801 low in the hippocampus. These results reveal highly dynamic changes in the c-Fos activation pattern induced by NMDAR antagonists during puberty. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Division of Paediatric Endocrinology, University Children's Hospital Heidelberg, Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Inta
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia.
authors.forename: Emese
authors.initials: E
authors.lastname: Domonkos
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Natascha
authors.initials: N
authors.lastname: Pfeiffer
authors.affiliation: Max-Planck Research Group at the Institute for Anatomy and Cell Biology, University of Heidelberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.affiliation: Division of Paediatric Endocrinology, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Bettendorf
authors.affiliation: Department of Psychiatry (UPK), University of Basel, Switzerland.
authors.forename: Undine E
authors.initials: UE
authors.lastname: Lang
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany; Department of Psychiatry (UPK), University of Basel, Switzerland. Electronic address: Dragos.Inta@zi-mannheim.de.
authors.forename: Dragos
authors.initials: D
authors.lastname: Inta
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Gass
mesh_terms: D000375:Aging; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D016291:Dizocilpine Maleate
keywords: Cortex; Dentate gyrus; Gender; GluN2B; MK-801; Puberty