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Folia Neuropathologica
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1/2022
vol. 60
 
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abstract:
Original paper

Role of dopamine D3 receptors in methamphetamine-induced behavioural sensitization and the characterization of dopamine receptors (D1R–D5R) gene expression in the brain

Hongliang Su
1, 2
,
Xiao Wang
1
,
Junmei Bai
1
,
Yao Fan
1
,
Yan Du
3
,
Zhiwen Wei
1, 2
,
Jiangwei Yan
1
,
Keming Yun
1, 2
,
Teng Chen
4

  1. School of Forensic Medicine, Shanxi Medical University, Taiyuan, China
  2. Key Laboratory of Forensic Toxicology, Ministry of Public Security, Beijing, China
  3. School of Pharmaceutical Science, Shanxi Medical University, Taiyuan, China
  4. College of Forensic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, China
Folia Neuropathol 2022; 60 (1): 105-113
DOI: https://doi.org/10.5114/fn.2022.114021
Online publish date: 2022/03/29
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Introduction
As a central nervous system stimulant, methamphetamine (METH) can cause lasting changes after being abused, including possible changes of gene expression in the brain. The dopamine (DA) system plays a fundamental role in METH-induced behavioural changes, but the expression levels of various subtypes of DA receptors, especially the dopamine D3 receptor (D3R), remains unclear.

Material and methods
We explored the effect of the D3R on METH-induced behavioural sensitization by comparing D3R knockout (D3R-/-) mice with wild type (WT) mice. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the five DA receptor (D1R, D2R, D3R, D4R, and D5R) genes in four brain regions: the prefrontal cortex (PFc), nucleus accumbens (NAc), caudate-putamen (CPu), and hippocampus (Hip).

Results
The behavioural test results revealed that METH could induce behavioural sensitization both in WT and D3R-/- mice. Moreover, in D3R-/- mice, the increase in movement distance induced by methamphetamine was significantly less than that of wild-type mice. The response of the five DA receptors to METH exposure varies in different brain regions. To be more specific, METH increased the expression of the D3R gene in most brain regions of WT mice, decreased D1R and D2R gene expression both in the NAc and CPu of WT mice and in CPu of D3R-/- mice.

Conclusions
These results suggested that D3R may play a positive regulatory role in the locomotor effects of METH, and five DA receptors, especially D1R, D2R, and D3R, may concurrently participate in the adaptive changes and the regulation of METH-induced behavioural sensitization.

keywords:

methamphetamine, behavioural sensitization, dopamine receptor, qRT-PCR, mice, drug addiction, knockout, gene expression, brain region, adaptive changes
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