Prostaglandin D2 inhibits pentylenetetrazole-induced convulsions in rats by a serotonin-mediated mechanism.

Abstract

Prostaglandins (PGs) of the E series are known to exert anticonvulsant action in experimental animals. Earlier studies from this laboratory have indicated that PGE1 inhibits pentylenetetrazole (PTZ)-induced convulsions in rats through a serotonin-mediated mechanism. PGD2, the major PG in the rodent brain, shares a number of central pharmacological actions of the PGEs, and like the latter it potentiates the anticonvulsant action of phenobarbitone and phenytoin in rats. The present study was undertaken to investigate the putative anticonvulsant action of PGD2 against PTZ-induced convulsions in rats and to evaluate the role of serotonin in the anticonvulsant action of PGD2. PGD2 (5, 10, and 20 micrograms, icv) produced a dose-related inhibition of PTZ-induced clonic convulsions in rats. The anticonvulsant action of PGD2 (20 micrograms, icv) was significantly attenuated following pretreatment of the rats with pharmacologic agents known to reduce central serotonergic activity, including 5,6-dihydroxytryptamine, a selective neurotoxin for serotonergic neurons, p-chlorophenylalanine, a specific inhibitor of serotonin biosynthesis, metergoline, a serotonin postsynaptic receptor antagonist, and quipazine, which is known to inhibit neuronal release of serotonin. These findings, in conjunction with an earlier study from this laboratory indicating that PGD2 augments rat brain serotonergic activity, suggest that the anticonvulsant activity of PGD2 against PTZ-induced convulsions in rats is mediated through a serotonergic mechanism.