Abstract
We found that centrally administered prostaglandin (PG) E2 exhibited anxiolytic-like activity in the elevated plus-maze and open field test in mice. Agonists selective for EP1 and EP4 receptors, among four receptor subtypes for PGE2, mimicked the anxiolytic-like activity of PGE2. The anxiolytic-like activity of PGE2 was blocked by an EP1 or EP4 antagonist, as well as in EP4 but not EP1 knockout mice. Central activation of either EP1 or EP4 receptors resulted in anxiolytic-like activity. The PGE2-induced anxiolytic-like activity was inhibited by antagonists for serotonin 5-HT1A, dopamine D1 and GABAA receptors. Taken together, PGE2 exhibits anxiolytic-like activity via EP1 and EP4 receptors, with downstream involvement of 5-HT1A, D1 and GABAA receptor systems.
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