Intracerebral injection of phospholipase A2 inhibits dopamine-mediated behavior in rats: possible implications for schizophrenia.

Abstract

Phospholipase A2 (PLA2) is a key enzyme in the phospholipid metabolism. In the CNS intracellular PLA2 plays an essential role in signal transduction by affecting both dopamine (DA) release and DA-receptor sensitivity. In schizophrenia a disordered phospholipid metabolism and increased activity of PLA2 have been reported. In this study we investigated the effects of intracerebral PLA2 injections on dopaminergic neurotransmission in rats using Ungerstedt's model of rotational behavior. Circling behavior induced by the DA agonist apomorphine after unilateral PLA2 injections into the substantia nigra pars compacta was recorded. Seven and 21 days after intranigral PLA2 injection, apomorphine induced an ipsilateral rotation indicating a long-lasting inhibition of ipsilateral nigrostriatal dopaminergic pathway by PLA2 application. In schizophrenia a reduced dopaminergic activity in the frontal cortex has been hypothesized. Recent spectroscopy studies reported on an accelerated break-down of membrane phospholipids in the frontal cortex from schizophrenics. The present findings suggest that increased PLA2 activity in schizophrenia could accelerate the breakdown of membrane phospholipids and thus contribute to a hypodopaminergy in the frontal cortex of schizophrenic patients.