Hyperthyroidism: Specifically increased response to central NA-(?-)receptor stimulation and generally increased monoamine turnover in brain

Abstract

SummaryRepeated treatment with thyroxine (T4) caused in mice enhanced response, i.e. locomotor stimulation, to central noradrenaline (NA)-receptor activation by clonidine but not to central dopamine (DA)-receptor activation by apomorphine or ET495 after previous depletion of endogenous catecholamines (CA) by reserpine and inhibition of the CA-synthesis by a-methyl-p-tyrosine. Increasing the dosese of the receptor agonists in control animals did not increase the locomotor stimulation but merely prolonged the effect. In chronically T4-treated rats with a significantly elevated plasma level of T4 and T8 the apomorphine-induced stereotypies were not increased and the response to small amounts of DA locally applied in N. accumbens was not significantly affected by the T4-pretreatment. The synthesis rates of NA and DA, reflected in the amount of L-Dopa accumulated in predominantly NA-and DA-rich brain parts, respectively, during 30 rain after administration of the centrally active, aromatic L-amino acid decarboxylase inhibitor NSD 1015, were both increased by T4-pretreatment. Also the brain serotonin (5-hydroxytryptamine, 5-HT)-synthesis was increased, measured in an analogous way. In contrast, utilization of brain CA or 5-HT seemed not affected by the T4-pretreatment, as disclosed by unchanged disappearance rates of NA, DA or 5-HT after inhibition of tyrosine hydroxylase and tryptophan hydroxylase, respectively. Release of brain CA, as reflected in the amount of O-methylated metabolites a~er monoamine oxidase inhibition, was not affected by the hormone pretreatment.We conclude that moderate hyperthyroidism is associated with a specific, increased sensitivity at or beyond central NA-(a-)receptors. This effect may be implicated in: 1. The potentiation by thyroid hormone of tricyclic antidepressive drugs; 2. the affective symptoms in hyperthyroidism, e.g. anxiety and increased susceptibility to emotional stress; 3. the cardiovascular symptoms in hyperthyroidism.

The effects of thyroid state on beta-adrenergic and serotonergic receptors in rat brain

“…However, opposite effects also have been reported (Engstrom et al, 1974. Jacoby et al, 1975Strombom et al, 1977), and it is not known whether the effects of thyroid hormones on this receptor or the 5HT 2 receptor population result from an adaptation to changes in synaptic level of endogenous ligands, stimulation of protein synthesis or other mechanisms.…”

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

“…Thyroid hormone application to euthyroid rodents increased cortical or whole brain 5-HT, 5-HTP and 5-HIAA concentrations in 10 studies. 41,[46][47][48][54][55][56][57][58][59] These results indicating increased cortical 5-HT turnover were consistent despite changing technologies over a 25-year period, and may be considered robust. In only one study did the whole brain 5-HT level not increase after thyroid hormone administration.…”

Thyroid hormones and the treatment of depression: An examination of basic hormonal actions in the mature mammalian brain

“…Thus, the observed changes in serotonin metabolism in hypothyroid and hyperthyroid rats are consistent with a generalized inverse relationship between serotonin metabolism and thyroid status although complex interactions with other factors are important as well. Opposite neurochemical findings to those obtained in the rat have been obtained in adult hyperthyroid mice, suggesting species variation (Engstom et al, 1975;Heal and Smith, 1988;Strombom et al, 1977).…”