Genetic deletion of the MT1 or MT2 melatonin receptors abrogates methamphetamine-induced reward in C3H/HeN mice.
Genetic deletion of the MT1 or MT2 melatonin receptors abrogates methamphetamine-induced reward in C3H/HeN mice.
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DOI：
10.1016/j.physbeh.2014.04.049
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发表时间：
2014-06-10
影响因子：
2.9
通讯作者：
Dubocovich ML
中科院分区：
文献类型：
--
作者：
Clough SJ;Hutchinson AJ;Hudson RL;Dubocovich ML
滥用药物甲基苯丙胺 (METH) 以其增强奖赏反应的能力而闻名。研究表明，精神兴奋剂的奖励特性在小鼠体内随一天中的不同时间而变化。本研究的目的是确定 MT1 和 MT2 褪黑激素受体在 METH 诱导的奖赏中的作用，通过明暗阶段的条件性位置偏好 (CPP) 范式进行测量。当内源性褪黑激素水平较低时，C3H/HeN 野生型小鼠在 ZT 6-8（ZT：Zeitgeber 时间；ZT 0 = 灯亮）或 ZT 19-21（当褪黑激素水平较高时）接受 METH 诱导的 CPP 训练。这些时间点也分别对应于昼夜节律基因Period1 表达的高点和低点。对 METH（1.2 mg/kg，腹腔注射）治疗的运动反应在两个时间点的强度相似，但是只有在 ZT 6-8 时接受 METH 的 C3H/HeN 小鼠才产生位置偏好。在 ZT 6-8 或 ZT 19-21 测试的具有 MT1 (MT1KO) 或 MT2 (MT2KO) 受体基因缺失的 C3H/HeN 小鼠并未对 METH 产生位置偏好，尽管与野生型小鼠相比，两种小鼠在 METH 治疗后均表现出类似的运动活性增加。我们的结论是，在我们的小鼠模型中，METH 诱导的条件性位置偏好取决于一天中的时间以及 MT1 或 MT2 受体的存在，这表明褪黑激素在 METH 诱导的奖励中发挥作用。
The drug of abuse methamphetamine (METH) is known for its ability to enhance reward responses. The rewarding properties of psychostimulants have been shown to vary across time of day in mice. The goal of this study was to determine the role of the MT1 and MT2 melatonin receptors in METH-induced reward, as measured by the conditioned place preference (CPP) paradigm during the light and dark phases. C3H/HeN wild-type mice were trained for METH-induced CPP at either ZT 6–8 (ZT: Zeitgeber time; ZT 0 = lights on), when endogenous melatonin levels are low, or ZT 19–21, when melatonin levels are high. These time points also correspond to the high and low points for expression of the circadian gene Period1, respectively. The locomotor response to METH (1.2 mg/kg, ip) treatment was of similar magnitude at both times, however only C3H/HeN mice conditioned to METH at ZT 6–8 developed a place preference. C3H/HeN mice with a genetic deletion of either the MT1 (MT1KO) or MT2 (MT2KO) receptor tested at ZT 6–8 or ZT 19–21 did not develop a place preference for METH, though both showed a similar increase in locomotor activity following METH treatment when compared to wild-type mice. We conclude that in our mouse model METH-induced conditioned place preference is dependent on time of day and the presence of the MT1 or MT2 receptors, suggesting a role for melatonin in METH-induced reward.