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Methamphetamine exacerbates neuroinflammatory response to lipopolysaccharide by activating dopamine D1-like receptors.

Abstract：

:Methamphetamine (METH) is a highly addictive and widely abused drug worldwide. Although much research is on the drug's direct effects, METH may also alter host immunity. The mechanism by which METH influences immunity remains elusive. Here, C57BL6/J mice were intraperitoneally injected with 5 mg/kg METH four times at two-hour intervals. The microglial inhibitor minocycline or dopamine D1-like receptor antagonist SCH-23390 was also applied prior to METH injection. Twenty-four hours following the first METH injection, mice were challenged by lipopolysaccharide (LPS) at a dose of 330 μg/kg, and the hippocampus (Hip), caudate putamen (CPU), nucleus accumbens (NAc) and prefrontal cortex (PFC) were collected 4 h after LPS administration. IL-6 and TNF-α levels were detected by ELISA. The activation of D1-like receptors and microglial marker Iba1 were examined by immunohistochemical staining and Western blot. Finally, we examined the phosphorylation of ERK1/2 and CREB. We found that METH exposure increased LPS-induced IL-6 and TNF-α production in the Hip, CPU and NAc regions. METH also augmented microglia activation and D1/5DR expression in response to LPS. Moreover, administering SCH-23390 significantly reduced IL-6 and TNF-α production and Iba1 expression following LPS challenge. Similar inhibitory effects were also observed by minocycline administration. Moreover, phosphorylation of ERK1/2 and CREB was increased after METH and LPS exposure but decreased by SCH-23390. These data illustrate that METH exacerbates neuroinflammation response in LPS-stimulated mouse brains through dopamine D1-like receptors, microglia, and relevant signaling proteins, which may have therapeutic implications.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Wang B,Chen T,Xue L,Wang J,Jia Y,Li G,Ren H,Wu F,Wu M,Chen Y

doi

10.1016/j.intimp.2019.04.053

subject

Has Abstract

pub_date

2019-08-01 00:00:00

pages

1-9

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(18)31189-5

journal_volume

73

pub_type

杂志文章

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