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Evaluation of the Relationship Between the Gene Expression Level of Orexin-1 Receptor in the Rat Blood and Prefrontal Cortex, Novelty-Seeking, and Proneness to Methamphetamine Dependence: A Candidate Biomarker Publisher Pubmed



Tavakkolifard M1 ; Vousooghi N1, 2, 3 ; Mahboubi S1 ; Golab F4 ; Ejtemaei Mehr S5 ; Zarrindast MR3, 5, 6
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Authors Affiliations
  1. 1. Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Research Center for Cognitive and Behavioral Sciences, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Iranian National Center for Addiction Studies (INCAS), Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Cognitive Neuroscience, Institute for Cognitive Science Studies, Tehran, Iran

Source: Peptides Published:2020


Abstract

Background: 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. Methods: 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. Results: 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. Conclusion: 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. © 2020 Elsevier Inc.
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