The Effects of Serotonin on Glucocorticoid Receptor Binding in Rat Raphe Nuclei and Hippocampal Cells in Culture

Authors

  • Micheline Héry,

    1. INSERUM U. 501, Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie, IFR Jean Roche, UER de Médecine Nord, Marseille, France
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  • Alexandra Sémont,

    1. INSERUM U. 501, Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie, IFR Jean Roche, UER de Médecine Nord, Marseille, France
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  • Marie-Pierre Fache,

    1. INSERUM U. 501, Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie, IFR Jean Roche, UER de Médecine Nord, Marseille, France
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  • Maxime Faudon,

    1. INSERUM U. 501, Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie, IFR Jean Roche, UER de Médecine Nord, Marseille, France
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  • Francis Héry

    1. INSERUM U. 501, Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie, IFR Jean Roche, UER de Médecine Nord, Marseille, France
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  • Abbreviations used: DOI, (±)-2,5-dimethoxy-4-iodoamphetamine; E, embryonic day; GR, glucocorticoid receptor; 5-HIAA, 5-hydroxyindoleacetic acid; 5-HT, serotonin; 8-OH-DPAT, (±)-8-hydroxy-2-(di-n-propylamino)tetralin; WAY 100135, N-tert-butyl-3-[1-[1-(2-methoxy)phenyl]piperazinyl]-1-phenylpropionamide.

Address correspondence and reprint requests to Dr. M. Héry at INSERM U. 501, Laboratoire des Interactions Fonctionnelles en Neuroendocrinologie, IFR Jean Roche, UER de Médecine Nord, Boulevard Pierre Dramard, 13916 Marseille Cedex 20, France. E-mail: herym@jean-roche.univ-mrs.fr

Abstract

Abstract: The raphe-hippocampal serotonin (5-HT) system is involved in the regulation of the hypothalamuspituitary-adrenal axis. The purpose of this study was to determine and compare the roles of 5-HT in the regulation of glucocorticoid receptor (GR) binding in the raphe nuclei and in the hippocampus. The effects of 5-HT, 5-HT agonists, and the 5-HT reuptake inhibitor citalopram on GR binding sites were studied in primary cultures of the fetal raphe nuclei and the hippocampus. Exposure of hippocampal cells to 5-HT, (±)-2,5-dimethoxy-4-iodoamphetamine (DOI; a 5-HT2 agonist), or citalopram resulted in an increase in number of GR binding sites. The effect of DOI was blocked by ketanserin (a 5-HT2 antagonist). Specific and saturable GR binding was found in raphe cells. Exposure of raphe cells to 5-HT, (±)-8 hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; a 5-HT1A agonist), or citalopram induced a significant decrease in number of GR binding sites. The effect of 8-OH-DPAT was reversed by WAY 100135 [N-tert-butyl-3-[1-[1-(2-methoxy)phenyl]piperazinyl]-1-phenylpropionamide; a 5-HT1A antagonist]. These results show that the regulation of GRs during fetal life is structure-dependent and involves different 5-HT receptor subtypes. Moreover, the regulation of hippocampal GRs by citalopram suggests an action of antidepressants independent of their effects on monoamines.

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