PT  - JOURNAL ARTICLE
AU  - Ryota Haba
AU  - Norihito Shintani
AU  - Yusuke Onaka
AU  - Takuya Kanoh
AU  - Hyper Wang
AU  - Risa Takenaga
AU  - Atsuko Hayata
AU  - Hiroyuki Hirai
AU  - Kin-ya Nagata
AU  - Masataka Nakamura
AU  - Atsushi Kasai
AU  - Ryota Hashimoto
AU  - Kazuki Nagayasu
AU  - Takanobu Nakazawa
AU  - Hitoshi Hashimoto
AU  - Akemichi Baba
TI  - Central CRTH2, a Second Prostaglandin D<sub>2</sub> Receptor, Mediates Emotional Impairment in the Lipopolysaccharide and Tumor-Induced Sickness Behavior Model
AID  - 10.1523/JNEUROSCI.1407-13.2014
DP  - 2014 Feb 12
TA  - The Journal of Neuroscience
PG  - 2514--2523
VI  - 34
IP  - 7
4099  - http://www.jneurosci.org/content/34/7/2514.short
4100  - http://www.jneurosci.org/content/34/7/2514.full
SO  - J. Neurosci.2014 Feb 12; 34
AB  - Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is a second prostaglandin D2 receptor involved in mediating the allergic response; however, its central function is not yet known. Here, we demonstrate that central CRTH2 mediates emotional impairment. Lipopolysaccharide (LPS)-induced decreases in social interaction and novel exploratory behavior were observed in wild-type (CRTH2+/+) mice but not CRTH2-deficient (CRTH2−/−) mice, but both genotypes showed hypolocomotion and anorexia following LPS injection. Tumor (colon 26) inoculation, a more pathologically relevant model, induced decreases in social interaction and novel exploratory behavior in CRTH2+/+, but not CRTH2−/− mice. In addition, the CRTH2 antagonists including clinically available ramatroban reversed impaired social interaction and novel exploratory behavior after either LPS or tumor inoculation in CRTH2+/+ mice. Finally, LPS-induced c-Fos expression in the hypothalamic paraventricular nucleus (PVN) and central amygdala (CeA) was selectively abolished in CRTH2−/− mice. These results show that CRTH2 participates in LPS-induced emotional changes and activation in the PVN and CeA. Our study provides the first evidence that central CRTH2 regulates specific emotional behaviors, and that CRTH2 antagonism has potential as a therapeutic target for behavioral symptoms associated with tumors and infectious diseases.