EFFECTS OF MODULATION OF NITRIC-OXIDE ON ACOUSTIC STARTLE RESPONDING AND PREPULSE INHIBITION IN RATS

The nitric oxide-arginine pathway is intimately connected to the relea se of dopamine and glutamate, two neurotransmitter systems that may be dysfunctional in schizophrenia. In addition, nitric oxide synthase in hibitors share several behavioral effects with the psychotomimetic dru g, phencyclidine. Previous research has found that phencyclidine-like drugs disrupt prepulse inhibition of the acoustic startle response, an animal model of sensorimotor gating, an attentional process that is d isrupted in certain neuropsychiatric disorders in humans (e.g., acute schizophrenia). The purpose of the present study was to examine the ef fects of nitric oxide modulators in this model. Following injection wi th a nitric oxide modulator or phencyclidine, rats were placed in star tle chambers in which they were exposed to acoustic pulses presented a lone or preceded by a prepulse. As in previous reports, phencyclidine disrupted prepulse inhibition at doses that did not affect startle dur ing pulse alone trials. In contrast, the nitric oxide synthase inhibit ors, N-G-nitro-L-arginine (L-NOARG) and N-G-nitro-L-arginine methyl es ter (L-NAME), dose-dependently decreased startle during pulse alone tr ials, but neither drug affected prepulse inhibition. A nitric oxide pr ecursor, L-arginine, produced similar results. Sodium nitroprusside (a nitric oxide releaser) and 7-nitroindazole (a third nitric oxide synt hase inhibitor) did not affect startle amplitudes during pulse alone o r prepulse + pulse trials. The present results suggest that modulation of nitric oxide synthesis or availability does not disrupt sensorimot or gating of the acoustic startle response and is probably not involve d in mediation of this type of attentional deficit in humans. (C) 1997 Elsevier Science B.V.