Dopamine D4 receptors elevated in schizophrenia

@article{Seeman1993DopamineDR,
  title={Dopamine D4 receptors elevated in schizophrenia},
  author={Philip Seeman and H C Guan and Hubert H.M. Van Tol},
  journal={Nature},
  year={1993},
  volume={365},
  pages={441-445}
}
ALTHOUGH the biological basis of schizophrenia is not known, possible causes include genetic defects, viruses1, amines2, brain structure and metabolism3–5, neuroreceptors6–8, and G proteins9. The hypothesis of dopamine overactivity in schizophrenia is based on the fact that neuroleptics block dopamine D2 receptors in direct relation to their clinical antipsychotic potencies10–11. Moreover, dopamine D2 or D2-like receptors are elevated in postmortem schizophrenia brain tissue8,12,13. This… 

Distribution of putative D4 dopamine receptors in postmortem striatum from patients with schizophrenia

  • A. MurrayT. Hyde J. Kleinman
  • Biology, Psychology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1995
TLDR
These findings suggest that the putative D4 receptors are not synthesized in this region, but are presynaptically localized on striatal afferent terminals, which is inconsistent with mRNA studies that have shown negligible amounts in striatum and accumbens.

The Importance of Dopamine D4 Receptors in the Action and Development of Antipsychotic Agents

TLDR
There is little to support the development of D4 antagonists as potential antipsychotic agents, and the report of an increase in D4 receptor density in the striatum in schizophrenia has not been consistently confirmed.

Dopamine D4 receptor variant, D4GLYCINE194, in Africans, but not in Caucasians: no association with schizophrenia.

TLDR
None of the 147 Caucasians (113 controls; 34 schizophrenics) revealed this variant, termed D4GLYCINE194, which occurs one amino acid away from a serine amino acid which is critical for the attachment of dopamine.

The dopamine D4 receptor in schizophrenia: an update

TLDR
The overall D2 characteristics, plus the anomalous divergence from these characteristics, make the D4 receptor a highly attractive candidate for the dopamine receptor abnormality of schizophrenia.

Are Striatal Dopamine D4 Receptors Increased in Schizophrenia?

TLDR
The increase in D2‐like receptor density in schizophrenia is due not to an increase in number of D4 sites in the disease, but to an up‐regulation of D2 or D3 receptors probably induced by chronic treatment with antipsychotic drugs.

Dopamine D2 and D4 receptor ligands: relation to antipsychotic action.

D4 dopamine receptor-mediated phospholipid methylation and its implications for mental illnesses such as schizophrenia

TLDR
It is shown that D4 dopamine receptors (D4R) mediate the stimulatory effect of dopamine (DA) on PLM, revealing a novel mechanism by which the D4R can regulate membrane composition.

Mesolimbic dopamine D3 receptors and use of antipsychotics in patients with schizophrenia. A postmortem study.

TLDR
Elevation of D3 receptor levels in limbic striatum and its efferents observed in patients with schizophrenia may be reduced by antipsychotic drugs.
...

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TLDR
The D1-D2 link may be mediated by guanine nucleotide-binding protein components influencing behavior, since the link was missing in over half the postmortem striata from patients with schizophrenia and Huntington disease but was present in human control, Alzheimer, and Parkinson striata.

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TLDR
An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.

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TLDR
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This is the first report of a receptor in the catecholamine receptor family that displays polymorphic variation in the human population and such variation among humans may underlie individual differences in susceptibility to neuropsychiatric disease and in responsiveness to antipsychotic medication.

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TLDR
The hypothesis of generally elevated central D2 dopamine receptor densities in schizophrenia was not supported by the present findings, and significantly higher densities were found in the left than in the right putamen but not in the caudate nucleus.

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TLDR
The densities of the two ligands were identical in Parkinson striata, indicating a low density (<1 pmol/g) for dopamine D4 receptors in the human striatum, consistent with other data indicating that clozapine does not have its major action in thehuman striatum.

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Direct evidence for some abnormalities in brain dopamine receptors in schizophrenia is obtained by measuring the specific binding of3H-apomorphine and 3H-haloperidol or 3H -spiperone to four regions of postmortem brains from schizophrenic patients.

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