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Mol Endocrinol. 2007 Nov;21(11):2795-804. Epub 2007 Jul 31.

Thyrotropin-releasing hormone receptor 1-deficient mice display increased depression and anxiety-like behavior.

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1
Omeros Corporation, 1420 Fifth Avenue, Suite 2600, Seattle, Washington 98101, USA. hongkuiz@alleninstitute.org

Abstract

TRH is a neuropeptide with a variety of hormonal and neurotransmitter/neuromodulator functions. In particular, TRH has pronounced acute antidepressant effects in both humans and animals and has been implicated in the mediation of the effects of other antidepressive therapies. Two G protein-coupled receptors, TRH receptor 1 (TRH-R1) and TRH-R2, have been identified. Here we report the generation and phenotypic characterization of mice deficient in TRH-R1. The TRH-R1 knockout mice have central hypothyroidism and mild hyperglycemia but exhibit normal growth and development and normal body weight and food intake. Behaviorally, the TRH-R1 knockout mice display increased anxiety and depression levels while behaving normally in a number of other aspects examined. These results provide the first direct evidence that the endogenous TRH system is involved in mood regulation, and this function is carried out through TRH-R1-mediated neural pathways.

PMID:
17666589
DOI:
10.1210/me.2007-0048
[Indexed for MEDLINE]
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