Background

Drug addiction is a chronically relapsing disorder in humans yet the underlying mechanism remained unclear. Recent studies suggested that histidine triad nucleotide binding protein1 (HINT1) may play significant roles in diverse neuropsychiatric diseases including drug addiction.

Methods

In the current study, we used different batches of mice to establish different stages of methamphetamine (METH)-induced behavioral sensitization (BS) to explore the dynamic changes throughout the process of addiction in different brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), and hippocampus (Hip). In addition, we used HINT1 knockout (KO) mice to investigate the effect of HINT1 protein deletion on METH-induced BS.

Results

We found that in PFC of the METH group mice, the HINT1 expression level initially increased after development phase, and then dropped to the normal level during expression phase. However, there was no statistical difference in the HINT1 expression level in the other three encephalic regions (NAc, CPu, and Hip). The absence of HINT1 could promote METH-mediated addictive behavior to a certain extent, while the significant difference between genotypes only occurred in the development phase.

Conclusions

Using the new technique, hip fractures were correctly predicted in 78% of cases compared with 36% when using the T-score. The accuracy of the prediction was not greatly reduced when using SSM and SAM (78% and 74% correct, respectively). Various geometric and BMD distribution traits were identified in the fractured and non-fractured groups.

中文翻译：

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HINT1在甲基苯丙胺诱导的行为敏化中的作用。

背景

吸毒成瘾是人类的一种慢性复发性疾病，但其潜在机制仍不清楚。最近的研究表明，组氨酸三联体核苷酸结合蛋白1（HINT1）可能在包括药物成瘾在内的多种神经精神疾病中发挥重要作用。

方法

在当前的研究中，我们使用了不同批次的小鼠建立了甲基苯丙胺（METH）诱导的行为敏化（BS）的不同阶段，以探索成瘾过程在不同大脑区域（包括前额叶皮层（PFC））中的动态变化，伏伏核（NAc），尾状壳核（CPu）和海马（Hip）。此外，我们使用HINT1基因敲除（KO）小鼠来研究HINT1蛋白缺失对METH诱导的BS的影响。

结果

我们发现，在METH组小鼠的PFC中，HINT1表达水平在发育阶段后开始升高，然后在表达阶段降至正常水平。但是，在其他三个脑区域（NAc，CPu和Hip）中，HINT1表达水平没有统计学差异。HINT1的缺失可以在一定程度上促进METH介导的成瘾行为，而基因型之间的显着差异仅发生在发育阶段。

结论

使用新技术，可以正确预测78％的病例发生髋部骨折，而使用T型评分的则为36％。使用SSM和SAM时，预测的准确性并没有大大降低（正确率分别为78％和74％）。在破裂组和非破裂组中鉴定出各种几何和BMD分布特征。