title: Disruption of the HPA-axis through corticosterone-release pellets induces robust depressive-like behavior and reduced BDNF levels in mice.
abstract: The corticosterone mouse model is widely used in preclinical research towards a better understanding of mechanisms of major depression. One particular administration procedure is the subcutaneous implantation of corticosterone slow-release pellets. In this report we want to provide basic evidence, regarding behavioral changes, neurotransmitter and -modulator levels and some other relevant biomolecules after hypothalamic-pituitary-adrenal-axis distortion. We show that three weeks of corticosterone pellet exposure robustly induces depressive-like but not anxiety-like behavior in mice, accompanied by a significant decrease in hippocampal brain-derived neurotrophic factor levels, at five weeks after the start of treatment. Furthermore there is an overall decrease in plasma corticosterone levels after three weeks of treatment that lasts up until the five weeks' time point. On the other hand, no differences are observed in total monoamine, glutamate or d-serine levels, nor in glucocorticoid receptor expression, in various depression-related brain areas. Altogether this characterization delivers vital information, supplementary to existing literature, regarding the phenotyping of pellet-induced hypothalamic-pituitary-adrenal-axis disruption in mice following three weeks of continuous corticosterone exposure.
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: Demuyser
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Eduard
authors.initials: E
authors.lastname: Bentea
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Lauren
authors.initials: L
authors.lastname: Deneyer
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Giulia
authors.initials: G
authors.lastname: Albertini
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology (MICH), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Massie
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium. Electronic address: Ilse.Smolders@vub.ac.be.
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000008:administration & dosage* / Q000097:blood; D003863:Depression / Q000139:chemically induced / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011965:Receptors, Glucocorticoid; D012701:Serotonin; D018698:Glutamic Acid; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine
keywords: BDNF; Corticosterone; Depression; GR; Neurotransmitters; Pellet