Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice

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Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice. / Jørgensen, Christinna Vangsgaard; Jacobsen, Jacob P; Caron, Marc G; Klein, Anders Bue; Knudsen, Gitte M; Mikkelsen, Jens D.

In: Neuroscience Letters, Vol. 555, 25.10.2013, p. 118-22.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Jørgensen, CV, Jacobsen, JP, Caron, MG, Klein, AB, Knudsen, GM & Mikkelsen, JD 2013, 'Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice', Neuroscience Letters, vol. 555, pp. 118-22. https://doi.org/10.1016/j.neulet.2013.08.073

APA

Jørgensen, C. V., Jacobsen, J. P., Caron, M. G., Klein, A. B., Knudsen, G. M., & Mikkelsen, J. D. (2013). Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice. Neuroscience Letters, 555, 118-22. https://doi.org/10.1016/j.neulet.2013.08.073

Vancouver

Jørgensen CV, Jacobsen JP, Caron MG, Klein AB, Knudsen GM, Mikkelsen JD. Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice. Neuroscience Letters. 2013 Oct 25;555:118-22. https://doi.org/10.1016/j.neulet.2013.08.073

Author

Jørgensen, Christinna Vangsgaard ; Jacobsen, Jacob P ; Caron, Marc G ; Klein, Anders Bue ; Knudsen, Gitte M ; Mikkelsen, Jens D. / Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice. In: Neuroscience Letters. 2013 ; Vol. 555. pp. 118-22.

Bibtex

@article{90c1e727ac364241ab5020b01cbaa580,

title = "Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice",

abstract = "Transgenic mice with a knock-in (KI) of a tryptophan hydroxylase 2 (Tph2) R439H mutation, analogous to the Tph2 R441H single-nucleotide polymorphism originally identified in a late life depression cohort, have markedly reduced levels of 5-hydroxytryptamine (5-HT). These Tph2KI mice are therefore interesting as a putative translational model of low endogenous 5-HT function that allows for assessment of adaptive changes in different anatomical regions. Here, we determined 5-HT2A receptor binding in several brain regions using in vitro receptor autoradiography and two different radioligands. When using the 5-HT2A receptor selective antagonist radioligand (3)H-MDL100907, we found higher binding in the prefrontal cortex (10%, P=0.009), the striatum (26%, P=0.005), and the substantia nigra (21%, P=0.027). The increase was confirmed in the same regions with the 5-HT2A/C receptor agonist, (3)H-CIMBI-36 (2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine). 5-HT2A receptors establish heteromeric receptor complexes with metabotropic glutamate 2 receptors (mGluR2), but binding levels of the mGluR2/3 ligand (3)H-LY341495 were unaltered in brain areas with increased 5-HT2A receptor levels. These data show that in distinct anatomical regions, 5-HT2A receptor binding sites are up-regulated in 5-HT deficient mice, and this increase is not associated with changes in mGluR2 binding.",

keywords = "Amino Acids, Animals, Brain, Gene Knock-In Techniques, Mice, Mice, Transgenic, Radioligand Assay, Receptor, Serotonin, 5-HT2A, Receptors, Metabotropic Glutamate, Tryptophan Hydroxylase, Up-Regulation, Xanthenes",

author = "J{\o}rgensen, {Christinna Vangsgaard} and Jacobsen, {Jacob P} and Caron, {Marc G} and Klein, {Anders Bue} and Knudsen, {Gitte M} and Mikkelsen, {Jens D}",

year = "2013",

month = oct,

day = "25",

doi = "10.1016/j.neulet.2013.08.073",

language = "English",

volume = "555",

pages = "118--22",

journal = "Neuroscience letters. Supplement",

issn = "0167-6253",

publisher = "Elsevier Ireland Ltd",

}

RIS

TY - JOUR

T1 - Cerebral 5-HT2A receptor binding, but not mGluR2, is increased in tryptophan hydroxylase 2 decrease-of-function mice

AU - Jørgensen, Christinna Vangsgaard

AU - Jacobsen, Jacob P

AU - Caron, Marc G

AU - Klein, Anders Bue

AU - Knudsen, Gitte M

AU - Mikkelsen, Jens D

PY - 2013/10/25

Y1 - 2013/10/25

N2 - Transgenic mice with a knock-in (KI) of a tryptophan hydroxylase 2 (Tph2) R439H mutation, analogous to the Tph2 R441H single-nucleotide polymorphism originally identified in a late life depression cohort, have markedly reduced levels of 5-hydroxytryptamine (5-HT). These Tph2KI mice are therefore interesting as a putative translational model of low endogenous 5-HT function that allows for assessment of adaptive changes in different anatomical regions. Here, we determined 5-HT2A receptor binding in several brain regions using in vitro receptor autoradiography and two different radioligands. When using the 5-HT2A receptor selective antagonist radioligand (3)H-MDL100907, we found higher binding in the prefrontal cortex (10%, P=0.009), the striatum (26%, P=0.005), and the substantia nigra (21%, P=0.027). The increase was confirmed in the same regions with the 5-HT2A/C receptor agonist, (3)H-CIMBI-36 (2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine). 5-HT2A receptors establish heteromeric receptor complexes with metabotropic glutamate 2 receptors (mGluR2), but binding levels of the mGluR2/3 ligand (3)H-LY341495 were unaltered in brain areas with increased 5-HT2A receptor levels. These data show that in distinct anatomical regions, 5-HT2A receptor binding sites are up-regulated in 5-HT deficient mice, and this increase is not associated with changes in mGluR2 binding.

AB - Transgenic mice with a knock-in (KI) of a tryptophan hydroxylase 2 (Tph2) R439H mutation, analogous to the Tph2 R441H single-nucleotide polymorphism originally identified in a late life depression cohort, have markedly reduced levels of 5-hydroxytryptamine (5-HT). These Tph2KI mice are therefore interesting as a putative translational model of low endogenous 5-HT function that allows for assessment of adaptive changes in different anatomical regions. Here, we determined 5-HT2A receptor binding in several brain regions using in vitro receptor autoradiography and two different radioligands. When using the 5-HT2A receptor selective antagonist radioligand (3)H-MDL100907, we found higher binding in the prefrontal cortex (10%, P=0.009), the striatum (26%, P=0.005), and the substantia nigra (21%, P=0.027). The increase was confirmed in the same regions with the 5-HT2A/C receptor agonist, (3)H-CIMBI-36 (2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine). 5-HT2A receptors establish heteromeric receptor complexes with metabotropic glutamate 2 receptors (mGluR2), but binding levels of the mGluR2/3 ligand (3)H-LY341495 were unaltered in brain areas with increased 5-HT2A receptor levels. These data show that in distinct anatomical regions, 5-HT2A receptor binding sites are up-regulated in 5-HT deficient mice, and this increase is not associated with changes in mGluR2 binding.

KW - Amino Acids

KW - Animals

KW - Brain

KW - Gene Knock-In Techniques

KW - Mice

KW - Mice, Transgenic

KW - Radioligand Assay

KW - Receptor, Serotonin, 5-HT2A

KW - Receptors, Metabotropic Glutamate

KW - Tryptophan Hydroxylase

KW - Up-Regulation

KW - Xanthenes

U2 - 10.1016/j.neulet.2013.08.073

DO - 10.1016/j.neulet.2013.08.073

M3 - Journal article

C2 - 24055299

VL - 555

SP - 118

EP - 122

JO - Neuroscience letters. Supplement

JF - Neuroscience letters. Supplement

SN - 0167-6253

ER -

ID: 105588916

Department of Neuroscience