Phospholipase A2 activity is selectively decreased in the striatum of chronic cocaine users.

Dopamine-mediated stimulation of arachidonic acid metabolism, via activation of the phospholipid metabolizing enzyme phospholipase A2 (PLA2), has recently been implicated in dopamine neurotransmitter function. We examined the status of PLA2 in autopsied brain of 10 chronic users of cocaine, a dopamine reuptake inhibitor. PLA2 activity, assayed at pH 8.5 in the presence of Ca2+, was significantly (p < 0.01) decreased by 31% in the putamen of cocaine users (n = 10) compared with that in controls (n = 10), whereas activity was normal in the frontal and occipital cortices, subcortical white matter, and cerebellum. In contrast, calcium-independent PLA2 activity, assayed at pH 7.0, was normal in all brain regions examined. Our finding of altered PLA2 activity restricted to a region of high dopamine receptor density suggests that modulation of PLA2 may be involved in mediating some of the dopamine-related behavioral effects of cocaine and could conceivably contribute to dopamine-related processes in the normal brain.