617 Cholecystokininergic modulation of ventral tegmental dopaminergic inputs to the posterior nucleus accumbens in rats

Treatment with 100 μM adenosine triphosphate (ATP) for 120 min augmented migration of cultured rat microglia by about 4-fold. This augmentation was effectively reduced by 0.1–10 μM prostaglandin E2 (PGE2). PGE2-mediated reduction was reversed by the EP2 antagonist AH6809 at 10 μM. The EP2 agonist butaprost also reduced ATP-induced migration at 10 μM, whereas the EP1 agonist 17-phenyl trinor PGE2, the EP3 agonist sulprostone, and the EP4 agonist PGE1 alcohol all had no effect at 10 μM. In addition, ATP-induced migration was reduced by the adenylate cyclase activator forskolin at 100 μM, whereas the adenylate cyclase inhibitor SQ22536 reversed the effect of PGE2 on ATP-induced migration at 100 μM. Over the same experimental duration, PGE2, butaprost, and forskolin had little effect on cell viability. These findings indicate that ATP-induced microglial migration is reduced by PGE2 through EP2 and adenylate cyclase.