TIME-COURSE OF ALTERED THYROID STATES ON 5-HT(1A) 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 a ppears to be involved in the pathophysiology of mood disorders, the ti me course of the effects of thyroidectomy (TXT) with or without thyrox ine (T4) replacement on 5-HT1A receptors and 5-HT uptake sites was exa mined. TXT caused a significant increase in H-3-8-hydroxy-2-(di-n-prop ylamino)-tetralin (H-3-DPAT) binding to 5-HT1A receptors in the cortex and hippocampus at 7 days and this increase was also evident at 35 da ys following TXT. By contrast, TXT did not have a significant effect o n H-3-DPAT binding in the hypothalamus or in the dorsal raphe nucleus. TXT did not affect the binding of H-3-cyanoimipramine (H-3-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 ca used the binding of H-3-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 H-3-CN-IMI binding to 5-HT uptake sites when compared to sham-opera ted animals at all time points examined. These results suggest that a neuromodulatory link may exist between the HPT axis and 5-HT1A recepto rs in the limbic regions of the rat brain. Depending on the brain regi on examined, a differential response to circulating levels of thyroid hormone was observed.