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.
Tejani-Butt
S M
SM
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia.
Yang
J
J
Kaviani
A
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D006980:Hyperthyroidism / Q000139:chemically induced / Q000503:physiopathology; D007099:Imipramine / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011863:Radioimmunoassay; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology; D013961:Thyroid Gland / Q000502:physiology*; D013965:Thyroidectomy; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C024316:cianopramine; D014284:Triiodothyronine; D013779:Tetrodotoxin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007099:Imipramine; D013974:Thyroxine