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 release of dopamine and glutamate, two neurotransmitter systems that may be dysfunctional in schizophrenia. In addition, nitric oxide synthase inhibitors share several behavioral effects with the psychotomimetic drug, 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 disrupted in certain neuropsychiatric disorders in humans (e.g., acute schizophrenia). The purpose of the present study was to examine the effects of nitric oxide modulators in this model. Following injection with a nitric oxide modulator or phencyclidine, rats were placed in startle chambers in which they were exposed to acoustic pulses presented alone or preceded by a prepulse. As in previous reports, phencyclidine disrupted prepulse inhibition at doses that did not affect startle during pulse alone trials. In contrast, the nitric oxide synthase inhibitors, N(G)-nitro-L-arginine (L-NOARG) and N(G)-nitro-L-arginine methyl ester (L-NAME), dose-dependently decreased startle during pulse alone trials, but neither drug affected prepulse inhibition. A nitric oxide precursor, L-arginine, produced similar results. Sodium nitroprusside (a nitric oxide releaser) and 7-nitroindazole (a third nitric oxide synthase inhibitor) did not affect startle amplitudes during pulse alone or prepulse + pulse trials. The present results suggest that modulation of nitric oxide synthesis or availability does not disrupt sensorimotor gating of the acoustic startle response and is probably not involved in mediation of this type of attentional deficit in humans.
Wiley
J L
JL
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613, USA. jwiley@gems.vcu.edu
Golden
K M
KM
Bowen
S E
SE
D000161:Acoustic Stimulation; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D010622:Phencyclidine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester