title: Effects of experimental hypothyroidism on 5-HT1A, 5-HT2A receptors, 5-HT uptake sites and tryptophan hydroxylase activity in mature rat brain1.
abstract: The study was aimed at investigating the repercussions of deficiency in thyroid function with and without thyroid hormone (TH) replacement on the neurochemical entities which underly serotonin (5-HT) neutrotransmission, namely 5-HT1A, 5-HT2A receptors, 5-HT transporter and tryptophan hydroxylase (TPH) in the mature brain. Surgically thyroidectomized male Wistar rats received: (1) an iodine-free diet to produce severe hypothyroidism; (2) hormonal replacement with 15 microgram/kg/day of thyroxine (T4) for 21 days to normalize serum TH levels, or (3) hormonal replacement with 200 microgram/kg/day of T4 for 14 days to produce an excess of circulating THs. Sham-operated rats were used as controls. Neither hypothyroidism nor an excess in serum TH levels affected 3H-8-OH-DPAT binding to 5-HT1A receptors, 3H-citalopram binding to 5-HT transporter and TPH activity in various brain structures indicating that, in the mature brain, the presynaptic entities of 5-HT neurotransmission are resistant to large variations in TH levels. By contrast, hypothyroid rats had a significant decrease in Bmax of 3H-ketanserin binding to cortical 5-HT2A receptors compared to controls. Cortical 3H-ketanserin binding in thyroidectomized rats was normalized after replacement with low-dose T4. Excess serum TH levels in thyroidectomized rats did not produce any changes in cortical 5-HT2A receptors when compared to thyroidectomized rats with normalized TH levels. The present data suggest that the decrease in cortical 5-HT2A receptors is the main neurochemical event underlying the impairing effect of hypothyroidism on 5-HT neurotransmission.
authors.affiliation: INSERM U38, Fonction Thyroïdienne et Régulations, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Kulikov
authors.forename: X
authors.initials: X
authors.lastname: Moreau
authors.forename: R
authors.initials: R
authors.lastname: Jeanningros
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000502:physiology*; D015283:Citalopram / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism; D008163:Luminescent Measurements; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism; D013965:Thyroidectomy; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014365:Tryptophan Hydroxylase / Q000378:metabolism*
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015283:Citalopram; D007650:Ketanserin; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013974:Thyroxine; D014284:Triiodothyronine; D014365:Tryptophan Hydroxylase