Antagonism of ethanol ataxia by intracerebellar nicotine: Possible modulation by mouse cerebellar nitric oxide and cGMP
Antagonism of ethanol ataxia by intracerebellar nicotine: Possible modulation by mouse cerebellar nitric oxide and cGMP
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DOI：
10.1016/j.brainresbull.2005.12.002
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发表时间：
2006-03-31
影响因子：
3.8
通讯作者：
Dar, MS
中科院分区：
文献类型：
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作者：
Al-Rejaie, S;Dar, MS
我们以前曾报道，小脑内尼古丁减弱乙醇共济失调通过烟碱胆碱能受体。我们现在报告，小脑内尼古丁的乙醇共济失调的衰减调制小脑一氧化氮鸟苷酸环化酶（GC）信使系统。小脑内微输注SNP（硝普钠，一氧化氮供体; 15、30和60 pg）和SMT（S-甲基异硫脲; 70. 140.和280 fg;诱导型一氧化氮合酶的抑制剂）分别以剂量相关的方式显著增强和降低小脑内尼古丁诱导的乙醇共济失调的减弱。类似地，小脑内异甘草素（GC的激活剂; 1.2.和4pa）和ODQ（1H [1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮，GC抑制剂; 375、750和1500 fg）分别以剂量相关的方式显著增强和降低小脑内尼古丁诱导的乙醇共济失调减弱。这些结果表明，尼古丁和乙醇之间的功能相互作用可能涉及小脑一氧化氮和cGMP的调制。小脑内微量输注异甘草素（4. 8和16 pa）在不存在尼古丁的情况下，显著减弱乙醇共济失调，呈剂量依赖性，表明cGMP在乙醇共济失调中的强直性参与。最后，小脑内尼古丁（5 ng）显着增加，乙醇2 g/kg腹腔注射降低总小脑亚硝酸盐+硝酸盐（NOx）的水平，这是功能相关的乙醇共济失调和小脑内尼古丁的衰减。乙醇诱导的NOx减少，小脑内尼古丁显着拮抗。NOx数据进一步支持一氧化氮参与尼古丁和乙醇之间的行为相互作用。总之，本研究的结果表明，小脑一氧化氮信使系统和尼古丁和乙醇之间的行为相互作用的功能相关性。(c)2005年爱思唯尔公司All rights reserved.
We have reported previously that intracerebellar nicotine attenuates ethanol ataxia via nicotinic-cholinergic receptors. We report now that attenuation of ethanol ataxia by intracerebellar nicotine is modulated by cerebellar nitric oxide-guanylyl cyclase (GC) messenger system. Intracerebellar microinfusion of SNP (sodium nitroprusside, a nitric oxide donor; 15, 30, and 60 pg) and SMT (S-methylisothiourea; 70. 140. and 280 fg; an inhibitor of inducible nitric oxide synthase), significantly enhanced and reduced, respectively, intracerebellar nicotine-induced attenuation of ethanol ataxia in a dose-related manner. Similarly, intracerebellar isoliquiritigenin (an activator of GC; 1.2. and 4 pa) and ODQ (1 H [1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, an inhibitor of GC; 375, 750, and 1500 fg), significantly enhanced and reduced, respectively, intracerebellar nicotine-induced attenuation of ethanol ataxia in a dose-related fashion. These results suggest that the functional interaction between nicotine and ethanol may involve modulation by cerebellar nitric oxide and cGMP. Intracerebellar microinfusion of isoliquiritigenin (4. 8, and 16 pa) in the absence of nicotine significantly attenuated ethanol ataxia dose-dependently indicating a tonic involvement of cGMP in ethanol ataxia. Finally, intracerebellar nicotine (5 ng) significantly increased and ethanol 2 g/kg i.p. decreased levels of total cerebellar nitrite + nitrate (NOx) which were functionally correlated with ethanol ataxia and its attenuation by intracerebellar nicotine. The ethanol-induced decrease in NOx, was significantly antagonized by intracerebellar nicotine. The NOx data further supported an involvement of nitric oxide in the behavioral interaction between nicotine and ethanol. Overall, the results of the present investigation demonstrate a functional correlation between cerebellar nitric oxide messenger system and the behavioral interaction between nicotine and ethanol. (c) 2005 Elsevier Inc. All rights reserved.