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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >The response to naltrexone in ethanol-drinking rats depends on early environmental experiences.
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The response to naltrexone in ethanol-drinking rats depends on early environmental experiences.

机译：喝乙醇的大鼠对纳曲酮的反应取决于早期的环境经验。

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The opioid receptor antagonist naltrexone is currently used in the treatment of alcohol addiction. However, substantial individual differences have been reported for the efficacy of naltrexone. Genetic factors are known to contribute to these differences; however, little is known about the impact of early environmental influences. Based on previous findings that have suggested a link between ethanol, endogenous opioids and the early environment, it was hypothesised that early environmental factors affect naltrexone efficacy later in life. A population of Wistar rats was subjected to three different rearing conditions where the pups experienced a daily separation from the dam, for either 15 min or 360 min, or were just briefly handled. On postnatal day 26, the rats were given intermittent access to ethanol (5% and 20%) and water for six weeks before naltrexone (0.3mg/kg or 3.0mg/kg) or saline treatment using a randomised injection schedule with a one-week washout period between injections. Naltrexone reduced ethanol consumption, but there was high variability in the efficacy. In addition, there was an association between the rearing condition and the effectiveness of naltrexone. Naltrexone reduced ethanol intake in rats experiencing postnatal conditions that contrasted normal wildlife conditions, i.e., prolonged absence or continuous presence of the dam, and naltrexone had no effect on the total ethanol consumption in rats reared under naturalistic conditions, i.e., short absences of the dam. These rats reduced their intake of 5% ethanol but increased their preference for 20% ethanol. We conclude that rats with a history of early adversity responded well to naltrexone treatment, whereas rats reared in a social context similar to that found in nature did not benefit from treatment. The present study highlights the importance of not only considering genetics but also environmental factors when identifying individual responses to naltrexone.
机译：阿片受体拮抗剂纳曲酮目前用于治疗酒精成瘾。但是，据报道纳曲酮的疗效存在很大的个体差异。已知遗传因素可导致这些差异。但是，人们对早期环境影响的影响知之甚少。根据以前的发现，这些发现暗示了乙醇，内源性阿片类药物与早期环境之间的联系，据推测，早期环境因素会影响生命后期的纳曲酮疗效。一组Wistar大鼠经历了三种不同的饲养条件，其中幼犬每天与大坝分开，持续15分钟或360分钟，或者只是经过短暂处理。在出生后的第26天，在接受纳曲酮（0.3mg / kg或3.0mg / kg）或生理盐水治疗之前，大鼠应间歇性地使用乙醇（5％和20％）和水达6周，并采用随机注射方案，每次给药1次。两次注射之间的每周冲洗期。纳曲酮减少了乙醇的消耗，但疗效差异很大。此外，饲养条件与纳曲酮的有效性之间存在关联。纳曲酮减少了与正常野生动植物条件形成对比的出生后条件下大鼠的乙醇摄入量，即长期不存在或持续存在大坝，而纳曲酮对自然条件下饲养的大鼠（即短暂不存在大坝）的总乙醇消耗量没有影响。这些大鼠减少了5％乙醇的摄入，但增加了对20％乙醇的偏好。我们得出结论，具有早期逆境历史的大鼠对纳曲酮治疗反应良好，而在与自然界相似的社会环境中饲养的大鼠则无法从治疗中受益。本研究强调了在确定个体对纳曲酮的反应时不仅要考虑遗传因素而且要考虑环境因素的重要性。

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