- 作者: K. G. Akash; T. R. Anju; K. T. Peeyush; C. S. Paulose
- 作者服務機構: Molecular Neurobiology and Cell Biology Unit, Centre forNeuroscience, Department of Biotechnology, Cochin University of Science and Technology, Kerala, India
- 中文摘要: --
- 英文摘要: Dopamine D2 receptors are involved in ethanolself- administration behavior and also suggested to mediatethe onset and offset of ethanol drinking. In the presentstudy, we investigated dopamine (DA) content and DopamineD2 (DA D2) receptors in the hypothalamus and corpusstriatum of ethanol treated rats and aldehyde dehydrogenase(ALDH) activity in the liver and plasma of ethanoltreated rats and in vitro hepatocyte cultures. Hypothalamicand corpus striatal DA content decreased significantly(P\0.05, P\0.001 respectively) and homovanillic acid/dopamine (HVA/DA) ratio increased significantly(P\0.001) in ethanol treated rats when compared tocontrol. Scatchard analysis of [3H] YM-09151-2 binding toDA D2 receptors in hypothalamus showed a significantincrease (P\0.001) in Bmax without any change in Kd inethanol treated rats compared to control. The Kd of DA D2receptors significantly decreased (P\0.05) in the corpusstriatum of ethanol treated rats when compared to control.DA D2 receptor affinity in the hypothalamus and corpusstriatum of control and ethanol treated rats fitted to a singlesite model with unity as Hill slope value. The in vitrostudies on hepatocyte cultures showed that 10-5 M and10-7 M DA can reverse the increased ALDH activity in10% ethanol treated cells to near control level. Sulpiride,an antagonist of DA D2, reversed the effect of dopamine on10% ethanol induced ALDH activity in hepatocytes. Ourresults showed a decreased dopamine concentration withenhanced DA D2 receptors in the hypothalamus and corpusstriatum of ethanol treated rats. Also, increased ALDH wasobserved in the plasma and liver of ethanol treated rats andin vitro hepatocyte cultures with 10% ethanol as a compensatorymechanism for increased aldehyde productiondue to increased dopamine metabolism. A decrease indopamine concentration in major brain regions is coupledwith an increase in ALDH activity in liver and plasma,which contributes to the tendency for alcoholism. Since theadministration of 10-5 M and 10-7 M DA can reverse theincreased ALDH activity in ethanol treated cells to nearcontrol level, this has therapeutic application to correctethanol addicts from addiction due to allergic reactionobserved in aldehyde accumulation.
- 中文關鍵字: --
- 英文關鍵字: ALDH; Dopamine; Hypothalamus; Corpus striatum; Hepatocyte culture