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Mediating effect of dopamine D3 receptors on Jak2 and GABAAα1 expression in mouse brains induced by cocaine

摘要:

Background Cocaine addiction may involve complex neuroadaptations, including many changes of genes expression.Dopamine D3 receptors play an important role in cocaine addiction; however, its role in cocaine induced gene expression change is poorly understood. To identify the changes in gene expression induced by repeated cocaine exposure through D3 dopamine receptors, we compared the expression of four molecules: Janus kinase 2 (Jak2), g-aminobutanoic acid receptor subunit alpha 1 (GABAAα1), glutamate receptor AMPA3 alpha 3 (GluR 3) and stromal cell derived factor 1 (SDF1). These four have been implicated in mediating the actions of cocaine in the nucleus accumbens (NAc) and caudoputamen (CPu) in mice after acute and repeated cocaine exposure.Methods For the acute and repeated injections, the mice were divided into four groups: 30 mg/kg cocaine, nafadotride 0.5 mg/kg + cocaine 30 mg/kg, nafadotride 0.5 mg/kg, and saline as the basal group. The expression of Jak2, GABAAα1,GluR 3 and SDF1 were assayed by Western blot, quantitative real-time RT-PCR and immunohistochemistry.Results Twenty-four hours after seven consecutive days of repeated cocaine exposure, the expression of GABAAα1 decreased in cocaine group compared with basal line and further decreased in the cocaine + nafadotride group and remained at basal level in the nafadotride group. Similarly, the Jak2 expression decreased in cocaine group compared with base line. However, the levels of Jak2 increased in cocaine + nafadotride group compared with cocaine group, while remained at basal level in nafadotride group.Conclusions GABAAα1 and Jak2 may be involved in chronic cocaine induced neuroadaptations. D3 dopaminereceptors play an important role in the expression of these genes.

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作者单位: College of Traditional Chinese Medicine,Southern Medical University, Guangzhou 510515, China [1] Department of Pathophysiology, Key Laboratory of Guangdong Proteome Analysis, Key Laboratory for Transcriptomics and Proteomics,Ministry of Education,Southern Medical University, Guangzhou 510515, China [2] Department of Histology and Embryology,Southern Medical University, Guangzhou 510515, China [3] Laboratory of Molecular Immunology,Southern Medical University, Guangzhou 510515, China [4]
期刊: 《中华医学杂志(英文版)》2007年120卷10期 910-914页 SCIMEDLINEISTICCSCDBP
分类号: R9
栏目名称: ORIGINAL ARTICLES
发布时间: 2008-03-03
基金项目:
the grants from the Science Technology Research Project of Guangdong Province 广东省自然科学基金 the Medical Science Research Foundation of Guangdong Province
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