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

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Repeated 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 ET 495 after previous depletion of endogenous catecholamines (CA) by reserpine and inhibition of the CA-synthesis byα-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 T3 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 min 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 after 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-(α-)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.

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  1. D. M. Jackson

    Present address: Department of Pharmacology, University of Sydney, 2006, NSW, Australia

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  1. Departments of Pharmacology and Anatomy, University of Göteborg, Sweden

    U. Strömbom, T. H. Svensson, D. M. Jackson & G. Engström

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  1. U. Strömbom
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Strömbom, U., Svensson, T.H., Jackson, D.M. et al. Hyperthyroidism: Specifically increased response to central NA-(α-)receptor stimulation and generally increased monoamine turnover in brain. J. Neural Transmission 41, 73–92 (1977). https://doi.org/10.1007/BF01252966

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