Effect of fluoxetine, a serotonin reuptake inhibitor, on the pituitary-thyroid axis in rat.

Fluoxetine, a specific serotonin reuptake inhibitor, was administered i.p. either acutely or chronically (2 and 10 mg doses), and intraventricularly to normal rats. Basal TSH levels were measured and the pituitary TSH reserve was estimated by direct determination of pituitary TSH content and/or by a TRH test. Thyroxine (T4) and triiodothyronine (T3) serum levels were also measured. The acute administration elicited only a decrease in T4 levels, whereas the chronic administration resulted in a decrease in both T4 and T3 levels. The 10 mg acute and chronic administrations induced an increase in basal TSH and in pituitary TSH reserve. Intraventricular administration only prevented the initial stress-induced decline of serum TSH levels. The major effect of the drug seems to be stimulation of TSH synthesis and release via the inhibition of T4-mediated thyroid-pituitary feedback. Additionally, fluoxetine could exert a minor direct central stimulatory effect on TSH secretion.