Involvement of dopamine D3 receptor and dopamine transporter in methamphetamine-induced behavioral sensitization in tree shrews
- PMID:31943832
- PMCID: PMC7010569
- DOI: 10.1002/brb3.1533
Involvement of dopamine D3 receptor and dopamine transporter in methamphetamine-induced behavioral sensitization in tree shrews
Abstract
Introduction: This study aims to establish a methamphetamine (METH)-induced behavioral sensitization model using tree shrews, as well as to measure the protein expression of the dopamine D3 receptor (D3R) and dopamine transporter (DAT).
Methods: Forty tree shrews were equally and randomly divided into four experimental groups: those administered with 1, 2, and 4 mg/kg METH and a control group (treated with an equal amount of normal saline). Each experimental group was repeatedly exposed to METH for nine consecutive days to induce the development of behavioral sensitization, followed by four days of withdrawal (without the METH treatment) to induce the transfer of behavioral sensitization, then given 0.5 mg/kg of METH to undergo the expression of behavioral sensitization. Altered locomotor and stereotypic behaviors were measured daily via open-field experiments during the development and expression stages, and weight changes were also recorded. Then, the Western blot method was used to detect the expression levels of D3R and DAT in three brain regions: the nucleus accumbens, prefrontal cortex, and dorsal striatum 24 hr after the last behavioral test.
Results: METH administration augmented motor-stimulant responses and stereotypic behaviors in all experimental groups, and stereotypic behaviors intensified more in the groups treated with 2 and 4 mg/kg METH. Motion distance, speed, and trajectory were significantly elevated in all experimental, however, METH at 4 mg/kg induced more stereotypic behaviors, decreasing these locomotor activities as compared with the 2 mg/kg METH group. 2 and 4 mg/kg METH significantly upregulated and downregulated D3R and DAT expression levels, respectively, in three brain regions, and these changes are more pronounced in 2 mg/kg METH.
Conclusions: These results indicated that this animal model may be used to study the neurobiological mechanisms that underly the development and expression of behavioral sensitization to METH. Deregulated D3R and DAT expression may be involved in the METH-induced behavioral sensitization.
Keywords: METH; behavioral sensitization; dopamine D3 receptor; dopamine transporter; methamphetamine; tree shrews.
© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.
Conflict of interest statement
The authors declare no conflicts of interest.
Figures



Similar articles
- Levo-tetrahydropalmatine attenuates the development and expression of methamphetamine-induced locomotor sensitization and the accompanying activation of ERK in the nucleus accumbens and caudate putamen in mice.Zhao N, Chen Y, Zhu J, Wang L, Cao G, Dang Y, Yan C, Wang J, Chen T.Zhao N, et al.Neuroscience. 2014 Jan 31;258:101-10. doi: 10.1016/j.neuroscience.2013.11.025. Epub 2013 Nov 21.Neuroscience. 2014.PMID:24269936
- Role of dopamine D3 receptors in methamphetamine-induced behavioural sensitization and the characterization of dopamine receptors (D1R-D5R) gene expression in the brain.Su H, Wang X, Bai J, Fan Y, Du Y, Wei Z, Yan J, Yun K, Chen T.Su H, et al.Folia Neuropathol. 2022;60(1):105-113. doi: 10.5114/fn.2022.114021.Folia Neuropathol. 2022.PMID:35359150
- Methamphetamine-induced locomotor activity and behavioral sensitization: are dopamine d3 receptors involved?Jones CD, Bartee JA, Leite-Browning ML, Blackshear MA.Jones CD, et al.Cell Mol Biol (Noisy-le-grand). 2007 May 15;53(4):15-22.Cell Mol Biol (Noisy-le-grand). 2007.PMID:17531156
- [Identification of Piccolo as a regulator of behavioral plasticity and dopamine transporter internalization].Nitta A, Hibi Y, Miyamoto Y, Nabeshima T.Nitta A, et al.Nihon Arukoru Yakubutsu Igakkai Zasshi. 2010 Dec;45(6):525-9.Nihon Arukoru Yakubutsu Igakkai Zasshi. 2010.PMID:21387608Review.Japanese.
- Neuropsychotoxicity of abused drugs: involvement of matrix metalloproteinase-2 and -9 and tissue inhibitor of matrix metalloproteinase-2 in methamphetamine-induced behavioral sensitization and reward in rodents.Mizoguchi H, Yamada K, Nabeshima T.Mizoguchi H, et al.J Pharmacol Sci. 2008 Jan;106(1):9-14. doi: 10.1254/jphs.fm0070139. Epub 2008 Jan 16.J Pharmacol Sci. 2008.PMID:18198472Review.
Cited by
- Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.Miao L, Wang H, Li Y, Huang J, Wang C, Teng H, Xu L, Yang X, Tian Y, Yang G, Li J, Zeng X.Miao L, et al.Front Immunol. 2024 Aug 19;15:1423263. doi: 10.3389/fimmu.2024.1423263. eCollection 2024.Front Immunol. 2024.PMID:39224601Free PMC article.
- Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel.Huang J, Zhang R, Wang S, Zhang D, Leung CK, Yang G, Li Y, Liu L, Xu Y, Lin S, Wang C, Zeng X, Li J.Huang J, et al.Front Pharmacol. 2021 Mar 17;12:619436. doi: 10.3389/fphar.2021.619436. eCollection 2021.Front Pharmacol. 2021.PMID:33815104Free PMC article.
- Icariside II Attenuates Methamphetamine-Induced Neurotoxicity and Behavioral Impairments via Activating the Keap1-Nrf2 Pathway.Huang J, Ding J, Wang Z, Li Y, He Y, Wang X, Fan H, Xie Q, Qiu P.Huang J, et al.Oxid Med Cell Longev. 2022 Mar 28;2022:8400876. doi: 10.1155/2022/8400876. eCollection 2022.Oxid Med Cell Longev. 2022.PMID:35387263Free PMC article.
- Inflammasome Inhibition Prevents Motor Deficit and Cerebellar Degeneration Induced by Chronic Methamphetamine Administration.Ding J, Shen L, Ye Y, Hu S, Ren Z, Liu T, Dai J, Li Z, Wang J, Luo Y, Zhang Q, Zhang X, Qi X, Huang J.Ding J, et al.Front Mol Neurosci. 2022 Apr 1;15:861340. doi: 10.3389/fnmol.2022.861340. eCollection 2022.Front Mol Neurosci. 2022.PMID:35431795Free PMC article.
- The Adverse Effects of Prenatal METH Exposure on the Offspring: A Review.Li JH, Liu JL, Zhang KK, Chen LJ, Xu JT, Xie XL.Li JH, et al.Front Pharmacol. 2021 Jul 14;12:715176. doi: 10.3389/fphar.2021.715176. eCollection 2021.Front Pharmacol. 2021.PMID:34335277Free PMC article.Review.
References
- Annual report 2017: The situation of the drug problem in China (2018). Retrieved fromhttp://www.nncc626.com/2018-06/26/c_129901052.htm
Publication types
MeSH terms
Substances
Related information
Grants and funding
- 2018Y043/Scientific Research Fund of Education Department of Yunnan Province/International
- 2019S077/the Postgraduate Innovation Project of Kunming Medical University/International
- 81660310/National Nature Science Foundation of China/International
- 81960340/National Nature Science Foundation of China/International
- 81560303/National Nature Science Foundation of China/International
LinkOut - more resources
Full Text Sources
Medical