Prendergast M A, Terry A V, Jackson W J, Buccafusco J J
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 30912-2300, USA.
Pharmacol Biochem Behav. 1997 Jan;56(1):81-7. doi: 10.1016/S0091-3057(96)00160-8.
The gaseous neuromodulator nitric oxide (NO) is formed in brain regions known to mediate learning and memory processes. In rodent models, pharmacologic inhibition of NO synthesis impairs such processes. In the present study, N omega-nitro-L-arginine methyl ester (L-Name), an inhibitor of the constitutive form of the NO synthetic enzyme, was administered to seven non-aged, mature monkeys (Macaca Fascicularis, Macaca Mulatta, and Macaca Nemestrima) trained to perform a delayed matching-to-sample task (DMTS). L-Name (1.5, 25, and 50 mg/kg) produced marked decrements in task performance, as well as a reduction in the number of trials completed at the highest dose. This impairment of DMTS accuracy by the 50 mg/kg doses of L-Name appears to be associated with an aversive state marked by gastrointestinal disturbance and lethargy. The detrimental effects of the 25 mg/kg dose of L-Name on DMTS accuracy were completely blocked by concurrent administration of a mole-equivalent dose of the NO amino acid precursor L-arginine. As a whole, these data suggest that L-Name impairs processes involved in delayed recall in monkeys and that this impairment is associated with attenuated synthesis of NO. However, at higher doses (> or = 25 mg/kg) this impairment is associated with aversive effects of L-Name, possibly at both central and peripheral sites.
气态神经调质一氧化氮（NO）在已知介导学习和记忆过程的脑区中形成。在啮齿动物模型中，一氧化氮合成的药理抑制会损害这些过程。在本研究中，将NO合成酶组成型形式的抑制剂Nω-硝基-L-精氨酸甲酯（L-Name）给予七只未衰老的成年猴子（食蟹猴、恒河猴和黑冠猕猴），这些猴子经过训练可执行延迟匹配样本任务（DMTS）。L-Name（1.5、25和50mg/kg）导致任务表现显著下降，并且在最高剂量时完成的试验次数减少。50mg/kg剂量的L-Name对DMTS准确性的这种损害似乎与以胃肠功能紊乱和嗜睡为特征的厌恶状态有关。同时给予摩尔当量剂量的NO氨基酸前体L-精氨酸可完全阻断25mg/kg剂量的L-Name对DMTS准确性的有害影响。总体而言，这些数据表明L-Name损害了猴子延迟回忆所涉及的过程，并且这种损害与NO合成减弱有关。然而，在较高剂量（≥25mg/kg）时，这种损害与L-Name的厌恶效应有关，可能在中枢和外周部位均有影响。
