Central prostaglandin D(2) exhibits anxiolytic-like activity via the DP(1) 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 10-100pmol/mouse after intracerebroventricular (i.c.v.) administration in the elevated plus-maze test in mice. A DP(1) receptor-selective agonist, BW245C, mimicked the anxiolytic-like activity of PGD(2), while a DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) was inactive. The anxiolytic-like activity of PGD(2) was blocked by a DP(1) antagonist, BWA868C, suggesting that PGD(2)-induced anxiolytic-like activity was mediated by the DP(1) 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) and GABA(A) receptors, downstream of the DP(1) receptor.