Prostaglandin inhibition of apomorphine-induced circling in mice.

The effect of prostaglandins (PGs) on apomorphine (apo)-induced circling was examined in unilaterally lesioned mice. Intraventricularly injected PGD2, PGE2, and PGF2 alpha at a dose of 1.0 nmole/g all inhibited apo-induced circling. When injected directly into the striatum, these same PGs also inhibited circling in a dose range of 0.01-0.1 nmole/g, while the PGE2 metabolite, 13,14-dihydro-15-keto-PGE2, was inactive at 0.1 nmole/g. For both routes of administration, PGF2 alpha appeared to be the most potent of the PGs tested. PGs administered alone by either route to unilaterally lesioned mice did not produce circling. Pretreatment with the PG synthetase inhibitor, indomethacin, caused the apo treated mice to circle at significantly higher rates than control animals. These results are the first report suggesting that within dopamine (DA)-mediated pathways PGs act at sites postsynaptic to the dopaminergic synapse.