Dopaminergic Dysfunctions in Neonatal Hypothyroidism

  • Andrea Vaccari
  • Zvani L. Rossetti
Part of the Advances in Behavioral Biology book series (ABBI, volume 39)


It is well known that the nervous and the endocrine systems themselves communicate. Consistently, there exists a consensus that thyroid dysfunction may play a role in mental disorders.1 On the ground that impairment of central dopaminergic (DA) pathways may be relevant to the origin of some psychiatric disorders, the regulation of brain DA by thyroid hormones is generating much interest. In this connection, the present article dealing with the latter argument, will devote special attention to the early postnatal period, when the thyroid gland is necessary for brain maturation.


Congenital Hypothyroidism Penile Erection Corpus Striatum Cholinergic Interneuron Dopaminergic Dysfunction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. J. Prange, J. C. Garbutt, and P. T. Loosen, The hypothalamic-pituitary-thyroid axis in affective disorders, in: “Psychopharmacology: the Third Generation of Progress,” H. Y. Meltzer, ed., Raven Press, New York (1987).Google Scholar
  2. 2.
    A. Vaccari, Teratogenic mechanisms of dysthyroidism in the central nervous system, in: “Biochemical Basis of Functional Neuroteratology,” G. J. Boer et al., eds, Elsevier, Amsterdam (1988).Google Scholar
  3. 3.
    J. M. Manson, Teratogens, in: “Casarett and Doull’s Toxicology,” C. D. Klaassen et al., eds, MacMillan Publ. Co., New York (1986).Google Scholar
  4. 4.
    M. J. Ellenhorn and D. G. Barceloux, “Medical Toxicology,” Elsevier, New York (1988).Google Scholar
  5. 5.
    A. Vaccari, Z. L. Rossetti, G. De Mantis, E. Stefanini, E. Martino, and G. L. Gessa, Neonatal hypothyroidism induces striatal dopaminergic dysfunction, Neuroscience (in press).Google Scholar
  6. 6.
    C. R. Gerfen, K. G. Baimbridge, and J. Thibault, The neostriatal mosaic: III. Biochemical and developmental dissociation of patch-matrix mesostriatal systems, J.Neurosci. 7: 3935 (1987).PubMedGoogle Scholar
  7. 7.
    E. J. Lu and W. J. Brown, The developing caudate nucleus in the euthyroid and hypothyroid rat, J.Comp.Neurol. 171: 261 (1977).PubMedCrossRefGoogle Scholar
  8. 8.
    E. J. Lu and W. J. Brown, An electron microscopic study of the developing caudate nucleus in euthyroid and hypothyroid states, Anat.Embryol. 150: 335 (1977).PubMedCrossRefGoogle Scholar
  9. 9.
    J. T. Eayrs and S. Levine, Influence of thyroidectomy and subsequent replacement therapy upon conditioned avoidance learning in rats, J.Endocrinol. 25: 505 (1963).CrossRefGoogle Scholar
  10. 10.
    A. Ruiz-Marcos, F. Sanchez-Toscano, M. J. Obregon, F. E. Del Rey, and G. M. De Escobar, Thyroxine-treatment and recovery of hypothyroidism-induced pyramidal cell damage, Brain Res. 239: 559 (1982).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Ruiz-Marcos, J. Salas, F. Sanchez-Toscano, F. E. Del Rey, and G. M. De Escobar, Effect of neonatal and adult onset hypothyroidism on pyramidal cells of the rat auditory cortex, Devl Brain Res. 9: 205 (1982).CrossRefGoogle Scholar
  12. 12.
    R. Hebert, J. M. Langlois, and J. H. Dussault, Permanent defects in rat peripheral auditory function following perinatal hypothyroidism: determination of a critical period, Devl Brain Res. 23: 161 (1985).CrossRefGoogle Scholar
  13. 13.
    G. M. De Escobar and F. Escobar Del Rey, Thyroid hormone and the developing brain, in: “Congenital Hypothyroidism,” J.H. Dussault and P. Walker, eds, Academic Press, New York (1983).Google Scholar
  14. 14.
    R. Biassoni and A. Vaccari, Selective effects of thiol reagents on the binding sites for imipramine and neurotransmitter amines in the rat brain, Br.J.Pharmacol. 85: 447 (1985).PubMedGoogle Scholar
  15. 15.
    W. G. Beamer, E. M. Eicher, L. J. Maltais, and J. L. Southard, Inherited primary hypothyroidism in mice, Science 212: 61 (1981).PubMedCrossRefGoogle Scholar
  16. 16.
    W. G. Beamer and L. A. Creswell, Defective thyroid ontogenesis in fetal hypothyroid (hyt/hyt) mice, Anat.Rec. 202: 387 (1982).PubMedCrossRefGoogle Scholar
  17. 17.
    P. M. Adams, S. A. Stein, M. Palnitkar, A. Anthony, L. Gerrity, and D. R. Shanklin, Evaluation and characterization of the hypothyroid hyt/hyt mouse I: somatic and behavioral studies, Neuroendocrinol. 49: 138 (1989).CrossRefGoogle Scholar
  18. 18.
    R. L. Singhal, R. B. Rastogi, and P. D. Hrdina, Brain biogenic amines and altered thyroid function, Life Sci. 17: 1617 (1975).PubMedCrossRefGoogle Scholar
  19. 19.
    R. B. Rastogi, Y. La Pierre, and R. L. Singhal, Evidence for the role of brain biogenic amines in depressed motor activity seen in chemically thyroidectomized rats, J.Neurochem. 26: 446 (1976).CrossRefGoogle Scholar
  20. 20.
    J. Puymirat, Effects of dysthyroidism on central catecholaminergic neurons, Neurochem.Int. 7: 969 (1985).PubMedCrossRefGoogle Scholar
  21. 21.
    A. Vaccari, R. Biassoni, and P. S. Timiras, Selective effects of neonatal hypothyroidism on monoamine oxidase activities in the rat brain, J.Neurochem. 40: 1019 (1983).PubMedCrossRefGoogle Scholar
  22. 22.
    R. N. Kalaria and A. K. Prince, Effects of thyroid deficiency on the development of cholinergic, GABA, dopaminergic and glutamate neuron markers and DNA concentrations in the rat corpus striatum, Int.J. Devl.Neurosci. 3: 655 (1985).CrossRefGoogle Scholar
  23. 23.
    C. Atack, N. H. Bass, and P. Lundberg, Mechanisms for the elimination of 5-hydroxyindoleacetic acid for brain cerebrospinal fluid of the rat during postnatal development, Brain Res. 77: 111 (1974).PubMedCrossRefGoogle Scholar
  24. 24.
    A. Vaccari, High affinity binding of [3H]-tyramine in the central nervous system, Br.J.Pharmac. 89: 15 (1986).Google Scholar
  25. 25.
    A. Vaccari and G. L. Gessa, [3H]Tyramine binding: a com parison with neuronal [3H]dopamine uptake and [3H]mazindol binding processes, Neurochem.Res. 14: 949 (1989).PubMedCrossRefGoogle Scholar
  26. 26.
    J. A. Javitch, R. O. Blaustein, and S. H. Snyder, [3H]Mazindol binding associated with neuronal dopamine uptake sites in corpus striatum membranes, Eur. J.Pharmacol. 90: 461 (1983).PubMedCrossRefGoogle Scholar
  27. 27.
    R. E. Heikkila, B. S. Shapiro, and R. C. Duvoisin, The relationship between loss of dopamine nerve terminals, striatal [3H]spiroperidol binding and rotational behaviour in unilaterally 6-hydroxydopaminelesioned rats, Brain Res. 211: 285 (1981).PubMedCrossRefGoogle Scholar
  28. 28.
    A. Vaccari and P. S. Timiras, Alterations in brain dopaminergic receptors in developing hypo-and hyperthyroid rats, Neurochem.Int. 3: 149 (1981).PubMedCrossRefGoogle Scholar
  29. 29.
    J. Lehmann and S. Z. Langer, The striatal cholinergic interneuron: synaptic target of dopaminergic terminals? Neuroscience 10: 1105 (1983).PubMedCrossRefGoogle Scholar
  30. 30.
    S. E. Leff, L. Adams, J. Hyttel, and I. Creese, Kainate lesion dissociates striatal dopamine receptor ligand binding sites, Eur.J.Pharmac. 70: 71 (1981).CrossRefGoogle Scholar
  31. 31.
    F. M. Filloux, J. K. Wamsley, and T. M. Dawson, Presynaptic and postsynaptic D dopamine receptors in thenigrostriatal system of the rat brain: a quantitative autoradiographic study using the selective D antagonist [3H]SCH 23390, Brain Res. 408:205 (L987).Google Scholar
  32. 32.
    J. Arnt, Behavioral studies of dopamine receptors: evidence for regional selectivity and receptor multiplicity, in: “Dopamine Receptors,” I. Creese and C.M. Fraser, eds, Alan R. List, Inc., New York (1987).Google Scholar
  33. 33.
    D. H. Overstreet, A. D. Crocker, C. A. Lawson, G. M. McIntosh, and J. M. Crocker, Alterations in the dopaminergic system and behaviour in rats reared on iodine-deficient diets, Pharmacol.Biochem.Behay. 21: 561 (1984).CrossRefGoogle Scholar
  34. 34.
    M. R. Del Cerro, G. Somoza, S. Segovia, and A. Guillamon, Effects of neonatal thyroidectomy on neurotransmitter receptors in several regions of the rat brain, IRCS Med.Sci. 14: 92 (1986).Google Scholar
  35. 35.
    A. Vaccari, M. Collu, and G. Serra, Dopamine-mediated yawning and penile erections in neonatally-rendered hypothyroid rats: effects of GM: ganglioside, (sub-mitted).Google Scholar
  36. 36.
    G. Serra, M. Collu, P. D’Aquila, and G. L. Gessa, SKF 38393, a selective D1 DA agonist, induces penile erections in rats, Pharmacol.Res.Comm. 20: 247 (1988).CrossRefGoogle Scholar
  37. 37.
    G. Serra, M. Collu, and G. L. Gessa, Yawning is elicited by D2 dopamine agonists but is blocked by the D antagonist SCH 23390, Psvchopharmac. 91: 330 (1987).CrossRefGoogle Scholar
  38. 38.
    W. S. Schwark, Cretinism animal model: neonatal hypothyroidism in the rat, Am.J.Pathol. 87: 437 (1977).Google Scholar
  39. 39.
    C. E. Hendrich, W. J. Jackson, and S. P. Porterfield, Behavioral testing of progenies of Tx (hypothyroid) and growth hormone-treated Tx rats: an animal model for mental retardation, Neuroendocrinol. 38: 429 (1984).CrossRefGoogle Scholar
  40. 40.
    C. P. Comer and S. Norton, Behavioral consequences of perinatal hypothyroidism in postnatal and adult rats, Pharmacol.Biochem.Behay. 22: 605 (1985).CrossRefGoogle Scholar
  41. 41.
    B. S. Hetzel and I. D. Hay, Thyroid function, iodine nutrition and fetal brain development, Clin.Endocrinol.(Oxf.) 11: 445 (1979).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Andrea Vaccari
    • 1
  • Zvani L. Rossetti
    • 1
  1. 1.“B.B. Brodie” Department of NeuroscienceChair of Toxicology, Medical SchoolCagliariItaly

Personalised recommendations