Effects of olanzapine and paroxetine on phospholipase D activity in the rat brain.

Phospholipase D (PLD) plays a key role in a second messenger system producing phosphatidic acid, mediating, among others, serotonin 5-HT2 receptor activity. The aim of the study was to evaluate a possible effect of atypical antipsychotic drug, olanzapine (OLZ), and selective serotonin reuptake inhibitor (SSRI) antidepressant, paroxetine (PX), on oleate-activated PLD activity in plasma membranes isolated from rat brain cortex. PLD activity was determined using a fluorometric assay. Ritanserin was used to determine the 5-HT receptor mode of action. A single dose of 10 mmol/kg OLZ produced no change in rat brain cortex PLD activity, 20 mmol/kg OLZ caused a nonsignificant decrease, and long-term (21 days) administration of OLZ resulted in a 41.9% decrease in PLD activity. Single doses of PX significantly decreased PLD activity: 10 mmol/kg - by 28.6%; 20 mmol/kg - by 31.5%, and long-term (21 days) administration of PX - by 39.5%. The study indicates that the 5-HT2 receptor-mediated inhibition of oleate-activated PLD may be a common part of the mechanisms of action of OLZ and PX.