TY - JOUR T1 - Central CRTH2, a Second Prostaglandin D<sub>2</sub> Receptor, Mediates Emotional Impairment in the Lipopolysaccharide and Tumor-Induced Sickness Behavior Model JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2514 LP - 2523 DO - 10.1523/JNEUROSCI.1407-13.2014 VL - 34 IS - 7 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 Y1 - 2014/02/12 UR - http://www.jneurosci.org/content/34/7/2514.abstract N2 - 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. ER -