Tavakkolifard Mahnoosh, Vousooghi Nasim, Mahboubi Sara, Golab Fereshteh, Ejtemaei Mehr Shahram, Zarrindast Mohammad Reza
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Research Center for Cognitive and Behavioral Sciences, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran.
Peptides. 2020 Sep;131:170368. doi: 10.1016/j.peptides.2020.170368. Epub 2020 Jul 12.
previous studies have suggested that methamphetamine (METH) abuse may affect orexin regulation. However, the data regarding the relationship between the current level of orexin and the vulnerability to METH abuse are minimal. Here, we have investigated the correlation between the gene expression level of the orexin-1 receptor (OX1R) in the rat prefrontal cortex (PFC) and blood lymphocytes and susceptibility to METH dependence and its impact on novelty-seeking behavior.
male Wistar rats were first examined for novelty-seeking behavior by the novel object recognition test, and the expression level of OX1R in their blood lymphocytes was evaluated by real-time PCR. Then, the susceptibility to METH abuse was investigated by voluntary METH oral consumption test. According to the amounts of METH consumption, the animals were divided into two groups of METH preferring and non-preferring. Half of the rats in each group were sacrificed, and the level of OX1R in their blood lymphocytes and PFC tissue was measured. The other half were sacrificed for the same reason after two weeks of drug abstinence.
The indexes of novelty-seeking behavior were significantly higher in the METH- preferring group compared to the non-preferring animals. Furthermore, the expression level of OX1R in the blood lymphocytes and PFC in the preferring group was considerably higher than the non-preferring group.
Up-regulation of the mRNA expression level of OX1R in the lymphocytes and PFC may predict vulnerability to the METH consumption and novelty-seeking, which may serve as a potential biomarker for METH abuse.
先前的研究表明，甲基苯丙胺（METH）滥用可能会影响食欲素调节。然而，关于当前食欲素水平与METH滥用易感性之间关系的数据极少。在此，我们研究了大鼠前额叶皮质（PFC）和血液淋巴细胞中食欲素-1受体（OX1R）的基因表达水平与METH依赖易感性及其对新奇寻求行为的影响之间的相关性。
首先通过新物体识别测试检查雄性Wistar大鼠的新奇寻求行为，并通过实时PCR评估其血液淋巴细胞中OX1R的表达水平。然后，通过自愿口服METH测试研究对METH滥用的易感性。根据METH的摄入量，将动物分为METH偏好组和非偏好组。每组一半的大鼠被处死，测量其血液淋巴细胞和PFC组织中OX1R的水平。另一半在停药两周后因同样原因被处死。
与非偏好组动物相比，METH偏好组的新奇寻求行为指标显著更高。此外，偏好组血液淋巴细胞和PFC中OX1R的表达水平明显高于非偏好组。
淋巴细胞和PFC中OX1R mRNA表达水平的上调可能预示着对METH消费和新奇寻求的易感性，这可能作为METH滥用的潜在生物标志物。
