Serotonin stimulates hypothalamic mRNA expression and local release of neurohypophysial peptides

H Jørgensen, A Kjaer, U Knigge, M Møller, J Warberg

76 Citations (Scopus)

Abstract

The neurotransmitter serotonin (5-HT) stimulates the secretion of vasopressin and oxytocin, and 5-HT is involved in the mediation of the vasopressin and oxytocin response to stress. In male Wistar rats, we investigated the 5-HT receptors involved in the 5-HT-induced increase of mRNA expression of vasopressin and oxytocin in the hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The 5-HT precursor, 5-hydroxytryptophan, injected in combination with the 5-HT reuptake inhibitor, fluoxetine, increased oxytocin mRNA expression in the PVN, and the concentration of vasopressin and oxytocin in plasma, whereas mRNA in the SON was not affected. Intracerebroventricular infusion of 5-HT agonists selective for the 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptor increased oxytocin mRNA in the SON and PVN. Infusion of agonists selective for the 5-HT2A + 2C receptor increased vasopressin mRNA in the PVN, whereas none of the 5-HT agonists affected vasopressin mRNA in the SON. All the 5-HT agonists infused increased peripheral oxytocin concentration and vasopressin was increased by stimulation of the 5-HT2A, 5-HT2C and 5-HT3 receptor. Intracerebroventricular infusion of 100 nmol 5-HT increased the extracellular hypothalamic concentration of vasopressin as measured by microdialysis in the PVN. To evaluate the involvement of hypothalamic-pituitary system in the 5-hydroxytryptophan and fluoxetine-induced vasopressin secretion, rats were immunoneutralized with a specific anti-corticotropin-releasing hormone antiserum. This treatment reduced plasma vasopressin and oxytocin responses. We conclude that stimulation with 5-hydroxytryptophan or 5-HT agonists increases mRNA expression of oxytocin in the PVN and the SON via stimulation of at least 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors. Vasopressin mRNA in the PVN was increased only via the 5-HT2 receptor, whereas vasopressin mRNA in the SON does not seem to be affected by 5-HT stimulation. Corticotropin-releasing hormone appears to be partly involved in the mediation of 5-HT induced vasopressin and oxytocin secretion.

Original languageEnglish
JournalJournal of Neuroendocrinology
Volume15
Issue number6
Pages (from-to)564-71
Number of pages8
ISSN0953-8194
DOIs
Publication statusPublished - Jun 2003
Externally publishedYes

Keywords

  • Animals
  • Corticotropin-Releasing Hormone/metabolism
  • Fluoxetine/pharmacology
  • Gene Expression Regulation
  • Male
  • Oxytocin/biosynthesis
  • Paraventricular Hypothalamic Nucleus/drug effects
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin/classification
  • Serotonin/physiology
  • Serotonin Receptor Agonists/pharmacology
  • Selective Serotonin Reuptake Inhibitors/pharmacology
  • Supraoptic Nucleus/drug effects
  • Vasopressins/biosynthesis

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