Rationale

Methamnetamine (MNA; PAL-1046) is a new psychoactive substance that acts as a full biogenic amine transporter (BAT) substrate. BAT substrates promote neurotransmitter release from the nerve terminal and can be abused as stimulants. However, scientific information on the abuse potential of methamnetamine is lacking.

Objective

We evaluated the abuse liability of methamnetamine.

Methods

The effective dose range of methamnetamine was determined using a climbing behavior test. The rewarding effect and reinforcing effect of the test compound were evaluated in mice by conditioned place preference (CPP) testing and self-administration (SA) testing at the selected doses. Dopamine level changes were analyzed using synaptosomes and in vivo microdialysis to investigate the effects of methamnetamine on the central nervous system. Drug discrimination experiments were used to examine the potential similarity of the interoceptive effects of methamnetamine and cocaine.

Results

A significant response was observed in the climbing behavior test with 10 and 40 mg/kg intraperitoneally administered methamnetamine. In the CPP test, mice intraperitoneally administered methamnetamine (10 and 20 mg/kg) showed a significant preference for the drug-paired compartment. In the SA test, mice that intravenously received 1 mg/kg/infusion showed significant active-lever responses. Dopamine was significantly increased in synaptosomes and in in vivo microdialysis tests. Furthermore, methamnetamine showed cross-generalization with cocaine in a dose-dependent manner.

Conclusions

Methamnetamine exhibits interceptive stimulus properties similar to those of cocaine and induces rewarding and reinforcing effects, suggesting its dependence liability potential.

中文翻译：

---

评估甲基苯丙胺在啮齿动物中的滥用潜力：行为药理研究

基本原理

甲胺（MNA; PAL-1046）是一种新型精神活性物质，可作为完整的生物胺转运蛋白（BAT）底物。BAT底物促进神经递质从神经末梢释放，可以被用作兴奋剂。但是，缺乏有关甲基苯丙胺潜在滥用的科学信息。

客观的

我们评估了甲基苯丙胺的滥用责任。

方法

使用攀爬行为测试确定甲胺的有效剂量范围。通过在选定剂量下的条件性位置偏好（CPP）测试和自我给药（SA）测试，在小鼠中评估了测试化合物的奖励作用和增强作用。使用突触小体和体内微透析来分析多巴胺水平的变化，以研究甲基苯丙胺对中枢神经系统的影响。药物歧视实验被用来检验甲胺丁胺和可卡因的互感作用的潜在相似性。

结果

在腹膜内施用甲胺四胺10和40 mg / kg的攀登行为测试中，观察到了显着的反应。在CPP测试中，腹膜内注射甲胺（10和20 mg / kg）的小鼠表现出对药物配对隔室的明显偏爱。在SA测试中，静脉内接受1 mg / kg /滴注的小鼠表现出明显的活动杆反应。在突触小体和体内微透析试验中，多巴胺显着增加。此外，甲基苯丙胺与可卡因的交叉成矿作用呈剂量依赖性。

结论

甲基苯丙胺显示出与可卡因相似的拦截刺激特性，并产生奖励和增强作用，表明其具有潜在的依赖性责任。