Complement C5a exhibits anxiolytic-like activity via the prostaglandin D2-DP1 receptor system coupled to adenosine A2A and GABAA receptors.

We have recently found that central PGD(2) exhibits anxiolytic-like activity. Here we show that complement C5a exhibits anxiolytic-like activity via the PGD(2) system. Centrally administered C5a had anxiolytic-like activity at a dose of 0.3 pmol/mouse in the elevated plus-maze test in mice. C5a-induced anxiolytic-like activity was inhibited by indomethacin, a cyclooxygenase inhibitor, or BWA868C, an antagonist of DP(1) receptor for PGD(2), respectively. The anxiolytic effect of C5a was also blocked by SCH58261 or bicuculline, antagonists of adenosine A(2A) and GABA(A) receptors, respectively, which were activated downstream of PGD(2)-DP(1) receptor. These results suggest that C5a exhibits anxiolytic-like activity via the PGD(2)-DP(1) receptor system coupled to the activation of adenosine A(2A) and GABA(A) receptors.