NITRIC-OXIDE SYNTHASE INHIBITORS ATTENUATE PHENCYCLIDINE-INDUCED DISRUPTION OF PREPULSE INHIBITION

Glutamate stimulation of N-methyl-D-aspartate (NMDA) receptors results in release of nitric oxide which may mediate the effects of NMDA rece ptor stimulation and/or may result in feedback inhibition of the presy naptic neuron. Results of a previous study showed that nitric oxide sy nthase (NOS) inhibitors blocked dizocilpine-induced behavior in mice. In the present study, NOS inhibitors were tested in combination with p hencyclidine (PCP), a drug which typically dose-dependently disrupts p repulse inhibition of the acoustic startle response in rats. Alone, NO S inhibitors and promoters do not affect prepulse inhibition; however, when tested in combination with PCP, the NOS inhibitors, L-NOARG, 7-n itroindazole and arcaine-but not the NR2B-selective polyamine site NMD A antagonist, eliprodil-attenuated PCP-induced disruption of prepulse inhibition of the acoustic startle response. These effects are similar to those produced by many atypical antipsychotics and suggests that t his class of drugs should be investigated further for their potential utility as antipsychotics and as treatments for PCP abuse. (C) 1998 Am erican College of Neuropsychopharmacology. Published by Elsevier Scien ce Inc.