Central prostaglandin D2 exhibits anxiolytic-like activity via the DP1 receptor in mice

We found that prostaglandin (PG) D2, the most abundant PG produced in the central nervous system (CNS), exhibited anxiolytic-like activity at a dose of 10–100 pmol/mouse after intracerebroventricular (i.c.v.) administration in the elevated plus-maze test in mice. A DP1 receptor-selective agonist, BW245C, mimicked the anxiolytic-like activity of PGD2, while a DP2 receptor agonist 13,14-dihydro-15-keto-PGD2 was inactive. The anxiolytic-like activity of PGD2 was blocked by a DP1 antagonist, BWA868C, suggesting that PGD2-induced anxiolytic-like activity was mediated by the DP1 receptor. Adenosine A2A or GABAA receptor antagonists, SCH58261 or bicuculline, respectively, also blocked its anxiolytic-like activity. Taken together, centrally administered PGD2 may induce anxiolytic-like activity via the A2A and GABAA receptors, downstream of the DP1 receptor.