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首页> 外文期刊>Brain research >The potential anti-addictive agent, 18-methoxycoronaridine, blocks the sensitized locomotor and dopamine responses produced by repeated morphine treatment.
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The potential anti-addictive agent, 18-methoxycoronaridine, blocks the sensitized locomotor and dopamine responses produced by repeated morphine treatment.

机译：潜在的抗上瘾剂18-甲氧基Coronaridine会阻止通过重复吗啡治疗产生的敏化运动和多巴胺反应。

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18-Methoxycoronaridine (18-MC), a novel synthetic iboga congener, attenuates the reinforcing efficacy of morphine, disrupts some signs of morphine withdrawal in physically dependent rats and attenuates the dopamine response in the nucleus accumbens to acute morphine. The present study further investigated the interactions between 18-MC and morphine by examining the effects of 18-MC (40 mg/kg, i.p., 19 h earlier) on the expression of dopamine sensitization in the nucleus accumbens in response to morphine (20 mg/kg, i.p.) and on the dose-effect curves for morphine-induced locomotion (0-30 mg/kg, i.p.) in rats treated either acutely or repeatedly (five, once daily, injections of 20 mg/kg, i.p.) with morphine. Compared to vehicle pretreated controls, 18-MC increased the potency of morphine, shifting the dose-response curve to the left, in acute morphine treated rats; however, 18-MC did not alter the potency of morphine in rats treated repeatedly with morphine. Repeated morphine administration induced locomotor sensitization in approximately 50% of the rats tested; in vehicle pretreated rats, the morphine dose-response curve was shifted to the left in sensitized as compared to non-sensitized rats. In 18-MC pretreated rats, sensitized and non-sensitized rats responded similarly to morphine, revealing a blockade of sensitization by 18-MC. Consistent with this behavioural finding, 18-MC pretreatment completely abolished the sensitized dopamine response in the nucleus accumbens expressed by rats repeatedly treated with morphine. It is suggested that the potential anti-addictive efficacy of 18-MC might be related to an ability to restore normal functioning to a hypersensitive mesolimbic dopamine system produced by previous repeated morphine administration.
机译：一种新型的合成iboga同系物18-甲氧基冠心苷（18-MC）减弱了吗啡的增强功效，破坏了身体依赖性大鼠中吗啡戒断的某些症状，并减弱了伏隔核中对多巴胺的急性吗啡反应。本研究通过检查18-MC（40 mg / kg，腹腔注射，提前19 h）对伏安核中多巴胺敏化表达对吗啡（20 mg的反应）的影响，进一步研究了18-MC与吗啡之间的相互作用。 / kg，ip）和吗啡诱导的运动（0-30 mg / kg，ip）在急性或反复治疗（每天五次，每天注射20 mg / kg，ip）的大鼠中的剂量效应曲线吗啡。与媒介物预处理的对照组相比，在急性吗啡治疗的大鼠中，18-MC增加了吗啡的效力，使剂量反应曲线向左移动。然而，18-MC并不会改变吗啡反复治疗大鼠的吗啡效力。重复服用吗啡可引起大约50％的大鼠运动敏化;在载体预处理的大鼠中，与未致敏大鼠相比，致敏大鼠的吗啡剂量反应曲线向左移动。在18-MC预处理的大鼠中，敏化和未敏化的大鼠对吗啡的反应相似，显示出18-MC对敏化的阻断。与此行为发现一致，18-MC预处理完全消除了反复用吗啡治疗的大鼠所表达的伏隔核中的敏化多巴胺反应。建议18-MC的潜在抗成瘾功效可能与恢复先前重复使用吗啡产生的过敏性中脑边缘多巴胺系统正常功能的能力有关。

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