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Dopamine D 2 ‐Like Receptor Function is Converted from Excitatory to Inhibitory by Thyroxine in the Developmental Hippocampus
Author(s) -
OhNishi A.,
Saji M.,
Furudate S.I.,
Suzuki N.
Publication year - 2005
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2005.01381.x
Subject(s) - excitatory postsynaptic potential , glutamatergic , endocrinology , medicine , dopaminergic , inhibitory postsynaptic potential , dopamine , dopamine receptor , neurotransmission , neuroscience , receptor , hippocampal formation , chemistry , biology , glutamate receptor
The mechanism by which a lack of thyroid hormone in the early development of the brain causes permanent mental retardation in cretins is currently unknown. On the other hand, an abnormality in dopamine‐related brain function is believed to underlie some forms of mental illness. In this study, we demonstrate that although the activation of a dopaminergic D 2 ‐like receptor inhibited glutamatergic transmission in the hippocampal slices of normal adult rats, indicating the inhibitory action of the D 2 ‐like receptor on glutamatergic transmission, it markedly enhanced glutamatergic transmission both in a mutant hypothyroid rat with a missense mutation in thyroglobulin and in hypothyroid rats treated with methylmercaptoimidazole (MMI), indicating the excitatory action of the D 2 ‐like receptor on glutamatergic transmission. Paired pulse facilitation of field excitatory postsynaptic potentials was reduced by the activation of the D 2 ‐like receptors from MMI‐induced hypothyroid rats, suggesting a presynaptic locus of the excitatory action of the D 2 ‐like receptors. In normal rats, the excitatory D 2 ‐like dopamine receptors were observed in the developing stages and were completely replaced by normal inhibitory responses up to adulthood. Furthermore, the continuous supplement of thyroxine from birth exerted a normalising effect on the abnormal excitatory property of D 2 ‐like dopamine receptors in the hippocampal slices of MMI‐treated hypothyroid rats. From these results, it is suggested that thyroxine may play a crucial role in reversing the excitatory property of D 2 ‐like dopaminergic receptors in the immature brain to an inhibitory one in the mature brain. Moreover, we suggest that the abnormal excitatory property of D 2 ‐like dopaminergic receptors may develop in response to a lack of thyroxine and may contribute to some central nervous system deficits, including cognitive dysfunctions accompanied by hypothyroidism.