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.
Zhao
Hui
H
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto 611-0011, Japan.
Ohinata
Kousaku
K
Yoshikawa
Masaaki
M
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006827:Hydantoins / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D011457:Prostaglandins D / Q000494:pharmacology*; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D058917:Adenosine A2 Receptor Antagonists; D014151:Anti-Anxiety Agents; D058787:GABA-A Receptor Antagonists; D006827:Hydantoins; D011457:Prostaglandins D; D043705:Receptor, Adenosine A2A; D011963:Receptors, GABA-A; D011982:Receptors, Prostaglandin; C058848:BW A868C; D001640:Bicuculline