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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Long-term methadone treatment impairs novelty preference in rats both when present and absent in brain tissue.
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Long-term methadone treatment impairs novelty preference in rats both when present and absent in brain tissue.

机译：长期美沙酮治疗会损害大鼠脑组织中的新奇偏好。

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Behavioral consequences of long-term methadone treatment have received little attention either in humans or experimental animals. In this work, we show that methadone (2.5-10 mg/kg) administered (sc) once daily for three weeks with repeated withdrawal on Saturday and Sunday impairs the novelty preference in rats. One hour after the last injection, when methadone was still present in brain tissue, the rats were too affected by the sedative effects of the drug to perform the test. This was confirmed by an almost total lack of locomotor activity or exploratory behavior. One day after the last injection, the methadone treated rats showed a 70% reduction (p < 0.05) in novelty preference compared to rats administered saline. No methadone was detected in the brain tissue at this time. Moreover, there were no differences in locomotor activity or total exploratory behavior between the groups, indicating a specific impairment of cognitive functioning. In brain tissue, the methadone concentration versus time profile was shifted to the left after long-term treatment, indicating a change in uptake and distribution of the drug. The area under the two concentration versus time curves was, however, similar. Methadone disappeared completely from the brain within one day. Together, these results suggest that long-term methadone treatment may have a negative impact on cognitive functioning in rats, regardless of whether methadone is present in brain tissue.
机译：长期美沙酮治疗的行为后果在人类或实验动物中很少受到关注。在这项工作中，我们显示美沙酮（2.5-10 mg / kg）每天一次（sc）施用三周，在周六和周日反复停药会损害大鼠的新颖性。在最后一次注射后一小时，当脑组织中仍存在美沙酮时，该药的镇静作用对大鼠影响太大，无法进行测试。几乎完全缺乏运动活动或探索行为证实了这一点。在最后一次注射后的一天，与给予盐水的大鼠相比，用美沙酮治疗的大鼠在新颖性方面表现出降低了70％（p <0.05）。目前在脑组织中未检测到美沙酮。此外，两组之间的运动活动或总探索行为没有差异，表明认知功能有特定的损害。在脑组织中，长期治疗后，美沙酮浓度随时间变化的曲线向左移动，表明药物的吸收和分布发生了变化。然而，两条浓度对时间曲线下的面积相似。美沙酮在一天之内完全从大脑中消失。总之，这些结果表明，长期使用美沙酮可能会对大鼠的认知功能产生负面影响，而与脑组织中是否存在美沙酮无关。

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