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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Intracerebroventricular injection of antisense oligos to nNOS decreases rat ethanol intake.
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Intracerebroventricular injection of antisense oligos to nNOS decreases rat ethanol intake.

机译：脑室内向nNOS注射反义寡核苷酸可减少大鼠乙醇摄入量。

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摘要

Nitric oxide (NO) has been implicated in alcohol drinking behavior using NO synthase (NOS) inhibitors that are nonselective of the different isoforms of NOS. In the brain, there are two constitutive isoforms of NOS, neuronal NOS (nNOS) and endothelial NOS (eNOS). We used an antisense oligodeoxynucleotide directed against nNOS in ethanol dependent male Wistar rats to examine the specific contribution of nNOS in the control of ethanol intake. Rats were subjected to a free-choice situation water/ethanol (10% v/v) after chronic ethanol intoxication by inhalation of ethanol vapor. During the free-choice situation, rats were twice daily for 4 days intracerebroventricularly injected with either saline, or end-capped phosphorothioate-protected antisense or mismatch oligodeoxynucleotide (25 microg/4 microl per injection), or acamprosate (1 mg/kg body weight) as reference product for its anticraving properties. Our results showed that the antisense treatment, but not the mismatch treatment, reduced both ethanol intake and ethanol preference during treatment and posttreatment periods (by 25-30%) without alteration of the body weight gain. The antisense treatment, but not the mismatch treatment, also down-regulated nNOS mRNA levels (by 30%) and NOS activity in the hippocampus. The anticraving drug, acamprosate reduced both ethanol intake (by 58%) and ethanol preference. All these results suggest that nNOS is involved in the regulation of alcohol dependence.
机译：一氧化氮（NO）已与使用NO合酶（NOS）抑制剂的酒精饮用行为有关，NOS抑制剂对NOS的不同亚型没有选择性。在大脑中，有两种NOS的组成型亚型，即神经元NOS（nNOS）和内皮型NOS（eNOS）。我们在乙醇依赖的雄性Wistar大鼠中使用了针对nNOS的反义寡聚脱氧核苷酸，以检查nNOS在控制乙醇摄入中的特定作用。在慢性乙醇中毒后，通过吸入乙醇蒸气，使大鼠处于自由选择的状态下用水/乙醇（10％v / v）。在自由选择情况下，大鼠每天两次脑室内注射盐水，或封端的硫代磷酸酯保护的反义或错配寡聚脱氧核苷酸（每次注射25微克/ 4微升）或阿坎酸（1毫克/千克体重），连续4天）作为其抗渴特性的参考产品。我们的结果表明，在不改变体重增加的情况下，反义治疗（而不是错配治疗）在治疗期间和后治疗期间均减少了乙醇摄入和乙醇偏爱（降低25-30％）。反义治疗（而不是错配治疗）也下调海马中的nNOS mRNA水平（降低30％）和NOS活性。抗渴望药物阿坎酸降低了乙醇的摄入量（减少了58％）和乙醇的偏爱性。所有这些结果表明，nNOS参与了酒精依赖的调节。

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