Serotonin Stimulates Hypothalamic mRNA Expression and Local Release of Neurohypophysial Peptides

J Neuroendocrinol. 2003 Jun;15(6):564-71. doi: 10.1046/j.1365-2826.2003.01032.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • RNA, Messenger
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Vasopressins
  • Serotonin
  • Oxytocin
  • Corticotropin-Releasing Hormone