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

Background: phospholipase d (pld) plays a key role in a second messenger system producing phosphatidic acid,mediating,among others,serotonin 5-ht 2 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. methods: pldactivitywas determined using a fluorometric assay. ritanserinwas used to determine the 5-htreceptormode of action. results: asingle 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%. conclusion: 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. copyright © 2013 by institute of pharmacology polish academy of sciences.