Serotonin Stimulates Hypothalamic mRNA Expression and Local Release of Neurohypophysial Peptides

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.