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The role of HINT1 in methamphetamine-induced behavioral sensitization

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Abstract

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.

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Funding

This research is supported by grants from the National Science Foundation of China (No. 81771435 and No. 81171262), and Natural Science Basic Research Plan in Shaanxi Province of China (No. 2016JM8078).

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Authors and Affiliations

  1. College of Medicine & Forensics, Key Laboratory of the Health Ministry for Forensic Medicine, Key Laboratory of Environment and Genes Related to Diseases of the Education Ministry, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, China

    Gang Lei, Zheng Chu, Li-sha Deng, Liu Yang, Jun-liang He & Yong-hui Dang

  2. Department of Pharmacology and Toxicology, Institute of Basic Medicine Science, Xi’an Medical University, Xi’an, 710021, China

    Peng Liu

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  1. Peng Liu
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  2. Gang Lei
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  3. Zheng Chu
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  4. Li-sha Deng
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  5. Liu Yang
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  6. Jun-liang He
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  7. Yong-hui Dang
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Correspondence to Yong-hui Dang.

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The experimental protocol was approved by the Institutional Animal Care Committee of Xi’an Jiaotong University. All efforts were made to minimize the number of animals used and the distress experienced by the animals.

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The authors declare that they have no conflicts of interest.

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Liu, P., Lei, G., Chu, Z. et al. The role of HINT1 in methamphetamine-induced behavioral sensitization. Psychopharmacology 237, 2345–2351 (2020). https://doi.org/10.1007/s00213-020-05538-4

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  • DOI: https://doi.org/10.1007/s00213-020-05538-4

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