Time course of altered thyroid states on 5-HT1A receptors and 5-HT uptake sites in rat brain: an autoradiographic analysis.

Although a link between the hypothalamic-pituitary-thyroid (HPT) axis and affective disorder has been established, the mechanism underlying this relationship remains unclear. Since the serotonin (5-HT) system appears to be involved in the pathophysiology of mood disorders, the time course of the effects of thyroidectomy (TXT) with or without thyroxine (T4) replacement on 5-HT1A receptors and 5-HT uptake sites was examined. TXT caused a significant increase in 3H-8-hydroxy-2-(di-n-propylamino)-tetralin (3H-DPAT) binding to 5-HT1A receptors in the cortex and hippocampus at 7 days and this increase was also evident at 35 days following TXT. By contrast, TXT did not have a significant effect on 3H-DPAT binding in the hypothalamus or in the dorsal raphe nucleus. TXT did not affect the binding of 3H-cyanoimipramine (3H-CN-IMI) to 5-HT uptake sites in any of the brain regions analyzed, or at any of the time points studied. Administration of high-dose T4 for 28 days caused the binding of 3H-DPAT to recover to sham levels in the cortex, to increase in the hippocampus and hypothalamus, and had no effect in the dorsal raphe nucleus. Replacement with high-dose T4 had no effect on 3H-CN-IMI binding to 5-HT uptake sites when compared to sham-operated animals at all time points examined. These results suggest that a neuromodulatory link may exist between the HPT axis and 5-HT1A receptors in the limbic regions of the rat brain. Depending on the brain region examined, a differential response to circulating levels of thyroid hormone was observed.