Wiley J L, Golden K M, Bowen S E
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613, USA.
Eur J Pharmacol. 1997 Jun 11;328(2-3):125-30. doi: 10.1016/s0014-2999(97)83038-5.
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.
一氧化氮-精氨酸途径与多巴胺和谷氨酸的释放密切相关，这两种神经递质系统在精神分裂症中可能功能失调。此外，一氧化氮合酶抑制剂与拟精神病药物苯环己哌啶有几种行为效应相同。先前的研究发现，苯环己哌啶样药物会破坏听觉惊吓反应的前脉冲抑制，这是一种感觉运动门控的动物模型，在人类某些神经精神疾病（如急性精神分裂症）中，这种注意力过程会受到破坏。本研究的目的是在该模型中研究一氧化氮调节剂的作用。给大鼠注射一氧化氮调节剂或苯环己哌啶后，将它们置于惊吓室中，在惊吓室中它们会暴露于单独呈现的声脉冲或前有前脉冲的声脉冲。如先前报道，苯环己哌啶在不影响单独脉冲试验中的惊吓反应的剂量下破坏了前脉冲抑制。相比之下，一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸（L-NOARG）和N(G)-硝基-L-精氨酸甲酯（L-NAME）在单独脉冲试验中剂量依赖性地降低了惊吓反应，但两种药物均未影响前脉冲抑制。一氧化氮前体L-精氨酸产生了类似的结果。硝普钠（一种一氧化氮释放剂）和7-硝基吲唑（另一种一氧化氮合酶抑制剂）在单独脉冲试验或前脉冲+脉冲试验中均未影响惊吓幅度。目前的结果表明，一氧化氮合成或可用性的调节不会破坏听觉惊吓反应的感觉运动门控，可能也不参与人类这种注意力缺陷的介导。
