5‐HT6 receptor binding sites in schizophrenia and following antipsychotic drug administration: Autoradiographic studies with [125I]SB‐258585

@article{East20025HT6RB,
  title={5‐HT6 receptor binding sites in schizophrenia and following antipsychotic drug administration: Autoradiographic studies with [125I]SB‐258585},
  author={Simon Z. East and Philip Wj Burnet and Ronald A. Leslie and Jennifer C. Roberts and Paul J. Harrison},
  journal={Synapse},
  year={2002},
  volume={45}
}
The 5‐hydroxytryptamine (5‐HT; serotonin)‐6 receptor (5‐HT6R) is a putative target of atypical antipsychotic drugs and its mRNA expression is altered in schizophrenia. [125I]SB‐258585 is a selective 5‐HT6R antagonist which has been well characterized for use in the rat brain. The present study evaluated its suitability for receptor autoradiography in the human brain and its application to quantitative studies. The affinity (Kd ∼1.2 nM) and relative distribution of binding sites (striatum… Expand
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References

SHOWING 1-10 OF 55 REFERENCES
Expression of serotonin 5‐HT2A receptors in the human cerebellum and alterations in schizophrenia
TLDR
Cerebellar 5‐HT2AR gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5‐ HT2AR imaging studies which use the cerebellums as a reference region. Expand
Autoradiographic localization of 5‐HT2A receptors in the human brain using [3H]M100907 and [11C]M100907
TLDR
Detailed qualitative and quantitative information on the distribution of 5‐HT2A‐receptors in the human brain as well as reference information for the interpretation of previous initial results at much lower resolution in humans in vivo with PET and [11C]M100907 is provided. Expand
In vivo effects of the 5‐HT6 antagonist SB‐271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5‐HT, glutamate and aspartate
TLDR
The neurochemical effects of a selective 5‐HT6 receptor ligand are demonstrated for the first time using in vivo microdialysis in the freely moving rat by simultaneous measurement of 5‐hydroxytryptamine (5‐HT), dopamine, dopamine, noradrenaline, glutamate and aspartate from the striatum and frontal cortex. Expand
The distribution of 5-HT6 receptors in rat brain: an autoradiographic binding study using the radiolabelled 5-HT6 receptor antagonist [125I]SB-258585
TLDR
The striatal binding sites seen in this study may be on intrinsic GABAergic or cholinergic neurones, or on terminals of projection neurones from the thalamus or cerebral cortex, and suggest a possible involvement of 5-HT6 receptors in locomotor control, cognition, memory, and control of affect. Expand
5-HT1A and 5-HT2A Receptor mRNAs and Binding Site Densities Are Differentially Altered in Schizophrenia
TLDR
The data show that schizophrenia is associated with alterations in the expression of central 5-HT1A and5-HT2A receptors, and reveal more extensive decreases in 5- HT2A receptor gene expression at the mRNA level. Expand
Autoradiography with [3H]8-OH-DPAT reveals increases in 5-HT1A receptors in ventral prefrontal cortex in schizophrenia
TLDR
Schizophrenic patients, as compared with controls, had increased 5-HT(1A) receptor binding in the three orbital frontal regions examined, and were most apparent in the outer cortical laminae, consistent with the hypothesis that schizophrenia is associated with an abnormal glutamatergic afferent innervation of orbital frontal cortex. Expand
[3H]WAY–100635 for 5–HT1A receptor autoradiography in human brain: a comparison with [3H]8–OH–DPAT and demonstration of increased binding in the frontal cortex in schizophrenia
TLDR
Investigation of the use of [3H]WAY-100635 as a quantitative autoradiographic ligand in post-mortem human hippocampus, raphe and four cortical regions and compared it with the 5-HT1A receptor agonist, concluded that it is a valuable autoreadiography ligand for the qualitative and quantitative study of 5- HT1A receptors in the human brain. Expand
Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims.
TLDR
It is concluded that suicide is associated with a localized increase in 5-HT2 binding sites, which is linked to a deficiency in serotonin neurotransmission. Expand
Ionotropic Glutamate Receptor Modulation of 5-HT6 and 5-HT7 mRNA Expression in Rat Brain
TLDR
To the authors' knowledge, this is the first demonstration of the regulation of striatal 5-HT6 receptor mRNA expression, and provides neurochemical anatomical evidence for the interaction of serotonergic and glutamatergic systems. Expand
Characterization of [125I]‐SB‐258585 binding to human recombinant and native 5‐HT6 receptors in rat, pig and human brain tissue
SB‐258585 (4‐Iodo‐N‐[4‐methoxy‐3‐(4‐methyl‐piperazin‐1‐yl)‐phenyl]‐benzenesulphonamide) is a high affinity ligand at 5‐HT6 receptors. It displays over 100 fold selectivity for the 5‐HT6 receptor overExpand
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