Central PGE 2 exhibits anxiolytic‐like activity via EP 1 and EP 4 receptors in a manner dependent on serotonin 5‐HT 1A , dopamine D 1 and GABA A receptors

We found that centrally administered prostaglandin (PG) E 2 exhibited anxiolytic‐like activity in the elevated plus‐maze and open field test in mice. Agonists selective for EP 1 and EP 4 receptors, among four receptor subtypes for PGE 2 , mimicked the anxiolytic‐like activity of PGE 2 . The anxiolytic‐like activity of PGE 2 was blocked by an EP 1 or EP 4 antagonist, as well as in EP 4 but not EP 1 knockout mice. Central activation of either EP 1 or EP 4 receptors resulted in anxiolytic‐like activity. The PGE 2 ‐induced anxiolytic‐like activity was inhibited by antagonists for serotonin 5‐HT 1A , dopamine D 1 and GABA A receptors. Taken together, PGE 2 exhibits anxiolytic‐like activity via EP 1 and EP 4 receptors, with downstream involvement of 5‐HT 1A , D 1 and GABA A receptor systems.