@article {Haba2514, author = {Ryota Haba and Norihito Shintani and Yusuke Onaka and Takuya Kanoh and Hyper Wang and Risa Takenaga and Atsuko Hayata and Hiroyuki Hirai and Kin-ya Nagata and Masataka Nakamura and Atsushi Kasai and Ryota Hashimoto and Kazuki Nagayasu and Takanobu Nakazawa and Hitoshi Hashimoto and Akemichi Baba}, title = {Central CRTH2, a Second Prostaglandin D2 Receptor, Mediates Emotional Impairment in the Lipopolysaccharide and Tumor-Induced Sickness Behavior Model}, volume = {34}, number = {7}, pages = {2514--2523}, year = {2014}, doi = {10.1523/JNEUROSCI.1407-13.2014}, publisher = {Society for Neuroscience}, abstract = {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.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/34/7/2514}, eprint = {https://www.jneurosci.org/content/34/7/2514.full.pdf}, journal = {Journal of Neuroscience} }