EFFECTS OF PHENCYCLIDINE ON NITRIC-OXIDE SYNTHASE ACTIVITY IN DIFFERENT REGIONS OF RAT-BRAIN

Phencyclidine (PCP, Angel Dust) is a widely used drug of abuse and is known to have neurotoxic effects. PCP modulates N-methyl-D-aspartate ( NMDA) receptors and Ca2+-releasing pathways however, its mechanism of action and neurotoxic potential remain unclear. Nitric Oxide Synthase (NOS) is a Ca2+-dependent cytosolic enzyme involved in the biosynthesi s of nitric oxide (NO) which mediates several neuronal events. PCP in vitro at micromolar (5-100 mu M) concentrations significantly inhibite d NOS activity in rat cerebellum. Similar significant inhibition of NO S activity was also observed in the hippocampus, caudate nucleus, fron tal cortex and cerebellum of female rats (Sprague-Dawley) treated with PCP (15 mg/kg, ip) after 0.5, 1, 2, and 24 h. A time-dependent PCP-in hibition of NOS in different regions of the brain was observed up to 2 h however, POP-inhibited NOS activity was partially recovered at 24 h after treatment. These data suggest that PCP induced significant alte rations in NOS activity and interfered in NO-mediated neural signallin g processes.