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Chronic cocaine administration reduces phospholipase A(2) activity in rat brain striatum
1Highland Psychiatric Research Foundation, UHI Millenium Institute, Inverness, Scotland. brian@hprf.org.uk
Background:
Phospholipase A(2) (PLA(2)) catalyses the release of free fatty acids used for eicosanoid biosynthesis. We previously reported that calcium-stimulated PLA(2) activity is reduced in the brain of cocaine users and patients with schizophrenia, and have speculated that this is due to dopaminergic hyperactivity in both conditions.
Methods:
To investigate these observations under controlled conditions, PLA(2) activity was measured in brain of rats exposed to cocaine and the dopamine receptor antagonist haloperidol.
Results:
As compared with saline-treated controls, calcium-stimulated PLA(2) activity was reduced (-30%; P<0.01) in the dopamine-rich striatum of animals sacrificed 1 h after chronic (20 mg/kg/day) injection of cocaine, but was normal in haloperidol- (2 mg/kg/day) treated animals, and in the dopamine-poor cortex and cerebellum of animals treated with either drug.
Conclusion:
This confirms and extends our observations in human brain, and further suggests a link between the brain dopaminergic and phospholipid catabolic systems.