Intracerebroventricular injection of phospholipase A2 inhibits apomorphine-induced locomotion in rats.

Phospholipase A2 (PLA2) is a key enzyme in phospholipid metabolism. In neurons, membrane-bound PLA2 plays an essential role in signal transduction by affecting neurotransmitter release and receptor sensitivity. There are some reports of increased PLA2 activity in schizophrenia. We investigated the effects of intracerebroventricular (i.c.v.) injections of PLA2 on dopamine-mediated behavior in rats. Ten days after i.c.v. injection, PLA2 significantly inhibited apomorphine-induced locomotion as compared with i.c.v. saline injections. The inhibition of apomorphine-induced locomotion by PLA2 was reversible within 4 weeks after stereotaxic surgery. These findings suggest a functional inhibition of dopaminergic postsynaptic receptors by PLA2. Accelerated phospholipid metabolism and reduced dopaminergic activity in the prefrontal cortex have been postulated to play a role in schizophrenia. Increased PLA2 activity may be related to both abnormalities and could thus play a role in the pathophysiology of schizophrenia.