Wozniak K M, Pert A, Mele A, Linnoila M
Laboratory of Clinical Studies, DICBR, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Brain Res. 1991 Feb 1;540(1-2):31-40. doi: 10.1016/0006-8993(91)90489-i.
Dopaminergic systems are thought to play a major role in the stimulant and reinforcing properties of drugs of abuse, including ethanol. The present study describes the effects of local perfusion with ethanol (and other alcohols) on extracellular dopamine in the striatum and nucleus accumbens. Following the establishment of basal dopamine levels (2-3 h), various concentrations of ethanol in artificial CSF (0.01-10% v/v) were slowly perfused through a microdialysis probe. Each dose of ethanol was found to increase dopamine concentrations in both the striatum and nucleus accumbens. This increase was dose-related in the striatum. The exclusion of calcium and inclusion of 12.5 mM magnesium in the perfusion medium prevented, or greatly attenuated the ethanol-induced dopamine (DA) release. Thus, the release of DA by ethanol is exocytotic in nature and involves calcium-dependent processes. The other alcohols tested, namely methanol and butanol, demonstrated a structure-activity relationship together with ethanol, in their ability to increase extracellular DA. The relative potency was butanol greater than ethanol greater than methanol. The diffusion of ethanol into the brain tissue was investigated following perfusion through the probe. Relatively low concentrations of ethanol were found in striatal tissue during perfusion and they declined rapidly with time, following the removal of ethanol from the perfusate. The concentrations of ethanol achieved in brain tissue following focal application through the microdialysis probe were relevant to human intoxication.
多巴胺能系统被认为在包括乙醇在内的滥用药物的刺激和强化特性中起主要作用。本研究描述了用乙醇（和其他醇类）局部灌注对纹状体和伏隔核细胞外多巴胺的影响。在建立基础多巴胺水平（2 - 3小时）后，将不同浓度的乙醇（0.01 - 10% v/v）在人工脑脊液中通过微透析探针缓慢灌注。发现每剂乙醇都会增加纹状体和伏隔核中的多巴胺浓度。这种增加在纹状体中与剂量相关。在灌注介质中排除钙并加入12.5 mM镁可防止或大大减弱乙醇诱导的多巴胺（DA）释放。因此，乙醇诱导的DA释放本质上是胞吐作用，并且涉及钙依赖性过程。所测试的其他醇类，即甲醇和丁醇，在增加细胞外DA的能力方面与乙醇表现出结构 - 活性关系。相对效力为丁醇大于乙醇大于甲醇。在通过探针灌注后，研究了乙醇向脑组织中的扩散。在灌注期间，纹状体组织中发现相对较低浓度的乙醇，并且在从灌注液中去除乙醇后，它们随时间迅速下降。通过微透析探针局部应用后在脑组织中达到的乙醇浓度与人体中毒有关。
