Time Course of Altered Thyroid States on 5-HT_1A Receptors and 5-HT Uptake Sites in Rat Brain: An Autoradiographic Analysis

Abstract

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.

Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain

“…Studies on the density of 5-HT 1A (postsynaptic) receptors outside the brainstem yielded contradictory results. An increase in cortical and hippocampal 5-HT 1A (postsynaptic) receptors was observed by Tejani-Butt et al 50 but not by Hong et al 49 and Kulikov et al, 51 who found no significant differences compared to euthyroid adult rodents.…”

“…In experimentally-induced hypothyroid states the 5-HT 1A (presynaptic) receptor density in the brainstem and midbrain was not altered [49][50][51][52] (Table 1). Studies on the density of 5-HT 1A (postsynaptic) receptors outside the brainstem yielded contradictory results.…”

Thyroid hormone regulates Na+currents in cultured hippocampal neurons from postnatal rats

“…Although there is evidence that thyroid hormones selectively regulate a limited set of genes, the direct targets of thyroid hormone action have not unambiguously been identified (Oppenheimer et al 1994). Thyroid hormones have been shown to influence the expression of a variety of transporters, enzymes and receptors involved in transmitter uptake, metabolism and detection (Honegger & Lenoir 1980 ;Patel et al 1980 ;Atterwill et al 1984 ;Dussault & Ruel 1987 ;Tejani-Butt et al 1993) of some cytoskeletal proteins (e.g. Aniello et al 1991) and neurotrophins (e.g.…”

Neurotransmitters Level in Hypothyroid Male Albino Rats after Isotretinoin Treatment

“…In hypothyroid rats there are was a marked decrease of NE and DA as well as 5HT contents in most of the brain area examined (Table 2-5). Brain serotonin synthesis and turnover in rats was decreased in the sensitivity of serotonin receptors (Vaccari, 1982) and compensatory increase in the density of 5HT receptors, secondary to reduction in the level of synaptic serotonin (Tejani-Butt et al, 1993). Immunohistochemical studies in animal brains showed that T3 has high concentration in sinaptosomes, especially those located in noradrenergic neurotransmission brain nuclei (Dratman and Gordon, 1996).…”