Chronic effects of corticosterone on GIRK1-3 subunits and 5-HT1A receptor expression in rat brain and their reversal by concurrent fluoxetine treatment |
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| Authors: | Laura Saenz del Burgo Roser Cortés Guadalupe Mengod Mario Montaña Gontzal García del Caño Joan Sallés |
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| Affiliation: | 1. Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain;2. Department of Neurochemistry and Neuropharmacology, Institut d''Investigacions Biomèdiques de Barcelona (IIBB), CSIC-IDIBAPS, Barcelona, Spain;3. Department of Neurosciences, Faculty of Pharmacy, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain;4. Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain;5. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain;1. Mood Disorders Program (GRUDA), Institute and Department of Psychiatry, University of Sao Paulo, Brazil;2. Laboratory of Immunopharmacology, IBC, Federal University of Minas Gerais, Brazil;3. Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil;4. Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of São Paulo, Brazil;5. ETPB, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD, United States;1. Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain;2. Departamento de Psicobiología, Facultad de Psicología, UNED, 28040 Madrid, Spain;3. Departamento de Psicología Básica I, Facultad de Psicología, UNED, 28040 Madrid, Spain;4. Unidad de Investigación Traslacional, Hospital de Ciudad Real, Spain;1. Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia;2. Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia |
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| Abstract: | Dysregulation of the serotonergic system and abnormalities of the hypothalamic–pituitary–adrenal axis have been demonstrated in major depression. Animal studies indicate that 5-HT1A receptor expression may be reduced by long-term administration of corticosterone. However, similar studies on the regulation of GIRK channels, one of the most important effectors of the neuronal 5-HT1A receptor, are limited. In order to address these issues, slow-release corticosterone pellets were implanted subcutaneously to adrenal intact male rats (200 mg pellets, 35 days release). Starting on day 15, animals were treated for 21 days with fluoxetine (5 mg/kg/day, i.p.), or vehicle. Using in situ hybridization histochemistry and receptor autoradiography, we found that chronic corticosterone treatment was accompanied by a significant decrease on the mRNAs coding for mineralocorticoid receptors in hippocampal areas. Under these conditions, 5-HT1A receptor mRNA expression decreased in dorsal raphe nucleus and dentate gyrus. However, 5-HT1A receptor levels, as measured by [3H]-8-OH-DPAT binding, diminished significantly only in dentate gyrus. It is noteworthy that chronic treatment with fluoxetine reversed the alterations on 5-HT1A receptor mRNA levels only in dorsal raphe. Finally, chronic corticosterone treatment produced an increase on the mRNA coding for the GIRK2 subunit in several hypothalamic and thalamic areas, which was reversed by fluoxetine. Measurements of cell density and volume of the granular layer of the dentate gyrus did not reveal significant changes after corticosterone or corticosterone plus fluoxetine treatments. These data are relevant for a better understanding of the differential regulation of pre- and postsynaptic 5-HT1A receptors by corticosterone flattened rhythm. |
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