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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jørgensen, CV; Jacobsen, JP; Caron, MG; Klein, AB; Knudsen, GM; Mikkelsen, JD

Published Date

  • October 25, 2013

Published In

Volume / Issue

  • 555 /

Start / End Page

  • 118 - 122

PubMed ID

  • 24055299

Pubmed Central ID

  • 24055299

Electronic International Standard Serial Number (EISSN)

  • 1872-7972

Digital Object Identifier (DOI)

  • 10.1016/j.neulet.2013.08.073

Language

  • eng

Conference Location

  • Ireland