Chronic cocaine administration reduces phospholipase A(2) activity in rat brain striatum.
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.


CONCLUSIONS
This confirms and extends our observations in human brain, and further suggests a link between the brain dopaminergic and phospholipid catabolic systems.
Ross
B M
BM
Highland Psychiatric Research Foundation, UHI Millenium Institute, Inverness, Scotland. brian@hprf.org.uk
Turenne
S D
SD
D000217:Acyltransferases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003042:Cocaine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008245:Lysophospholipase / Q000378:metabolism; D008297:Male; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D000217:Acyltransferases; D010741:Phospholipases A; D008245:Lysophospholipase; D003042:Cocaine; D006220:Haloperidol; D002118:Calcium