Thyrotropin-releasing hormone receptor 1-deficient mice display increased depression and anxiety-like behavior.
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.
Zeng
Hongkui
H
Omeros Corporation, 1420 Fifth Avenue, Suite 2600, Seattle, Washington 98101, USA. hongkuiz@alleninstitute.org
Schimpf
Brian A
BA
Rohde
Alex D
AD
Pavlova
Maria N
MN
Gragerov
Alexander
A
Bergmann
John E
JE
D000339:Affect; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal; D001835:Body Weight; D003863:Depression / Q000378:metabolism*; D006943:Hyperglycemia / Q000235:genetics; D007037:Hypothyroidism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D009068:Movement; D010641:Phenotype; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000235:genetics* / Q000502:physiology*
D018025:Receptors, Thyrotropin-Releasing Hormone