title: Alteration of glutamate/GABA balance during acute alcohol intoxication in rats: effect of Xingnaojing injection.
abstract: BACKGROUND
  Xingnaojing Injection (XNJI) is a modern Chinese formula came from famous Chinese medicine An Gong Niu Huang Pill. XNJI has been used for treatment of cerebral diseases and stroke in China, and is approved by the State Food and Drug Administration of China for the treatment of acute alcohol intoxication (AAI). XNJI belongs to the ethnopharmacological family of medicines. In this study, we investigated the mechanisms of the XNJI effect on AAI.
  
  
  OBJECTIVE
  To investigate the effects of XNJI on glutamate, gamma-aminobutyric acid (GABA) and related receptor in lateral hypothalamic area (LHA) of AAI rat.
  
  
  METHODS
  Adult male Sprague-Dawley rats were implanted with microdialysis probes in LHA. Rats were randomly divided into control, model, 1.36mg/kg XNJI, 0.68mg/kg XNJI and 0.34mg/kg XNJI groups. During microdialysis, baseline samples were collected from 1h to 2.5h; thereafter, the rats were given an intraperitoneal injection of 52% ethanol, 5.2g/kg, or saline for control group. Twenty minutes later, three doses of XNJI was given by unilateral injection respectively, while saline for control and model groups, and samples were collected for the next 4h. The extracellular glutamate and GABA levels were measured in the LHA by a high performance liquid chromatography coupled with fluorescence detector (HPLC-FLU). The expression levels of related receptors N-methyl-d-aspartate receptor (NR) subunit NR2A, NR2B and GABAA were analyzed by reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Ethanol (5.2g/kg) significantly decreased the extracellular levels of glutamate and increased extracellular GABA in LHA. On the other hand ethanol significantly decreased NR2A and NR2B mRNAs expression, and increase GABAA mRNA expression. XNJI could increase the extracellular level of glutamate and decrease that of GABA; moreover, induced an increase in NR2A and NR2B mRNA expression, and a decrease in GABAA mRNA expression in LHA.
  
  
  CONCLUSIONS
  The current changes in glutamate, GABA and mRNA expressions of related receptors in LHA after injection of XNJI suggest that changes in these neurotransmitters and receptors as a potential mechanism of action for AAI.
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
authors: Jingjing
authors: J
authors: Wei
authors: School of Traditional Chinese Medicine Healthcare, Guangdong Food and Drug Vocational College, 321 Longdong North Road, Tianhe District, Guangzhou 510520, China.
authors: Limei
authors: L
authors: Yao
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
authors: Lei
authors: L
authors: Yang
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
authors: Wei
authors: W
authors: Zhao
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
authors: Si
authors: S
authors: Shi
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
authors: Qingyan
authors: Q
authors: Cai
authors: School of Traditional Chinese Medicine Healthcare, Guangdong Food and Drug Vocational College, 321 Longdong North Road, Tianhe District, Guangzhou 510520, China.
authors: Dingsheng
authors: D
authors: Chen
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China. Electronic address: liwr@gzucm.edu.cn.
authors: Weirong
authors: W
authors: Li
authors: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun District, Guangzhou 510405, China.
authors: Qi
authors: Q
authors: Wang
mesh_terms: D000435:Alcoholic Intoxication / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000431:Ethanol / Q000009:adverse effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008516:Medicine, Chinese Traditional / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C000594497:xingnaojing; D000431:Ethanol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Acute alcohol intoxication; GABA; Glutamate; Microdialysis; RT-PCR; Xingnaojing Injection