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

We found that prostaglandin (PG) D-2, 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 PGD(2) while a DP2 receptor agonist 13.14-dihydro-15-keto-PGD(2) was inactive, The anxiolytic-like activity of PGD(2) was blocked by a DP1 antagonist, BWA868C, suggesting that PGD(2)-induced anxiolytic-like activity was mediated by the DP1 receptor. Adenosine A(2A) or GABA(A) receptor antagonists, SCH58261 or bicuculline, respectively, also blocked its anxiolytic-like activity. Taken together,centrally administered PGD(2) may induce anxiolytic-like activity via the A(2A) acid GABA(A) receptors, downstream of the DP1 receptor. (C) 2008 Elsevier Inc. All rights reserved.