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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Pharmacologically targeting the P2rx4 gene on maintenance and reinstatement of alcohol self-administration in rats.
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Pharmacologically targeting the P2rx4 gene on maintenance and reinstatement of alcohol self-administration in rats.

机译：药理学上针对大鼠维持和恢复酒精自我给药的P2rx4基因。

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Genetic studies indicate that alcohol consumption associates with expression of the P2rx4 gene, a gene that codes for the P2X(4) receptor. This receptor is a subtype in the purinergic system of ligand-gated ion channels that when activated exerts excitatory effects in CNS. P2X(4) function is inhibited by alcohol and P2X(4) receptors are modulated positively by the antiparasitic agent, ivermectin. Two experiments were performed to test the ability of ivermectin to alter the behavioral effects of alcohol in rats. After alcohol exposure was achieved via the "drinking in the dark" procedure, separate groups of Sprague-Dawley rats were trained to lever press for either alcohol (10% ethanol/2% sucrose) or sucrose (3%) solutions in operant chambers. Rats were tested for maintenance of operant self-administration under a progressive ratio condition (Experiment 1) and for reinstatement of extinguished responding induced by solution presentation (Experiment 2) after ivermectin (0; 1-10mg/kg; IP) administration. Ivermectin decreased the amount of work that the animal performed to obtain reinforcers in the maintenance study, particularly in the group reinforced with alcohol, and tended to decrease reinstated lever press responding. Conditioned approach behavior (head entries) was significantly reduced by ivermectin in both experiments. Reduction in motor activity was seen during the longer maintenance sessions but not in the shorter reinstatement sessions. Results suggest some support for ivermectin-like drugs as potential treatment agents for alcohol dependence. Caution is warranted due to modest specificity on behavior reinforced by alcohol, some reduction in general activity levels, and the lack of dose-response effects.
机译：遗传研究表明，饮酒与P2rx4基因的表达有关，该基因编码P2X（4）受体。该受体是配体门控离子通道的嘌呤能系统的一种亚型，当激活时，它会在CNS中发挥兴奋作用。 P2X（4）功能被酒精抑制，P2X（4）受体被抗寄生虫药物伊维菌素正调控。进行了两个实验以测试伊维菌素改变大鼠酒精行为行为的能力。通过“在黑暗中饮酒”程序达到酒精暴露后，训练不同组的Sprague-Dawley大鼠以杠杆方式在手术室中挤压酒精（10％乙醇/ 2％蔗糖）或蔗糖（3％）溶液。在依维菌素（0; 1-10mg / kg; IP）给药后，测试大鼠在渐进比率条件下维持手术自我给药的维持（实验1）和恢复由溶液呈递诱导的熄灭的反应（实验2）。伊维菌素在维持性研究中减少了动物为获得增强剂而进行的工作量，尤其是在用酒精增强的动物中，并且趋于降低了恢复的杠杆压迫反应。伊维菌素在两个实验中均显着降低了有条件的进近行为（头部进入）。在较长的维护期间内，运动活动减少，而在较短的恢复期间内则未见。结果表明，对伊维菌素样药物作为潜在的酒精依赖治疗药物的支持。由于对酒精强化行为的适度专一性，一般活动水平的某些降低以及缺乏剂量反应效应，因此应谨慎。

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