High levels of calcium-independent phospholipase A(2) (iPLA(2)) are present in the striatum and cerebral cortex [W.Y. Ong, J.F. Yeo, S.F. Ling, A.A. Farooqui, Distribution of calcium-independent phospholipase A(2) (iPLA(2)) in monkey brain, J. Neurocytol. 34 (2005) 447-458], and several clinical investigations have suggested a possible role of altered iPLA(2) activity in neurodegenerative and psychiatric disorders. The present study was carried out to elucidate a possible effect of PLA(2) on prepulse inhibition (PPI) of the acoustic startle reflex. Rats that received intraperitoneal injection of the non-specific PLA(2) inhibitor, quinacrine, showed significantly decreased PPI at 76, 80, and 84dB, compared to saline injected controls. In addition, rats that received intrastriatal injection of antisense oligonucleotide to iPLA(2) showed significant reduction in PPI at prepulse intensities of 76 and 84dB compared to scrambled sense injected controls. Together, these findings point to a role of PLA(2) in PPI of the auditory startle reflex and sensorimotor gating.