Effects of combined administration of alcohol and abused drugs (methamphetamine, cocaine) on the central nervous system

我们用脑微透析方法研究了甲基安非他明（MAP）单次给药和乙醇（EtOH）和MAP联合给药对慢性酒精治疗大鼠纹状体细胞外多巴胺（DA）和血清素（5-HT）水平的影响。我们使用两种不同的高酒精偏好大鼠和低酒精偏好大鼠（分别为高酒精偏好大鼠（HAP）和低酒精偏好大鼠（LAP）），长期喂食含酒精的液体饮食6至8周。单次给药MAP后，LAP组纹状体DA和5-HT的变化百分比明显高于HAP组。然而，在酒精喂养组中，与LAP相比，酒精喂养HAP中DA和5-HT的变化百分比显着升高。在酒精喂养的LAP中，纹状体细胞外DA和5-HT没有显著增加。在MAP和EtOH联合给药的情况下，慢性酒精喂养大鼠的细胞外DA和5-HT水平在EtOH给药后略有升高，尤其是HAP。EtOH和MAP给药后，酒精喂养HAP中DA和5-羟色胺水平显著升高。这些百分比的变化比单次使用MAP观察到的要高。同时，LAP对长期给药EtOH和单一给药MAP的影响不太敏感。这些结果表明，当两种药物同时给药时，慢性EtOH治疗增强了HAP对MAP的敏感性，并且两种药物对滥用药物的反应性存在显著差异。在调查酒精和/或其他滥用药物的相互作用时，有必要考虑酒精偏好。

We have investigated the effects of single administration of methamphetamine (MAP) and of combined administration of ethanol (EtOH) and MAP on striatal extracellular dopamine (DA) and serotonin (5-HT) levels in chronic alcohol treated rats using a brain-microdialysis method. We used two different lines of rats with high and low alcohol preferences, (high alcohol preference rat (HAP) and low alcohol preference rat (LAP), respectively), which were chronically fed an alcohol containing liquid diet for 6 to 8 weeks.The percent change in DA and 5-HT in striatum following single administration of MAP was significantly higher in control-fed LAP than HAP. However, in the alcohol-fed group, the percent changes in DA and 5-HT were significantly elevated in the alcohol-fed HAP compared to LAP. There were no significant increases in striatal extracellular DA and 5-HT in alcohol-fed LAP.In combined administration of MAP and EtOH, extracellular DA and 5-HT levels increased slightly following EtOH administration in chronic alcohol-fed rats, especially in HAP. Dramatic increases of DA and 5-HT levels were observed in alcohol-fed HAP following EtOH and MAP administration. These percent changes ware higher than that observed with a single administration of MAP. Meanwhile, LAP were less sensitive to the influence of chronic EtOH administration and to single administration of MAP.These results demonstrate that a chronic treatment of EtOH enhances the sensitivity to MAP in a HAP, when two drugs were administrated simultaneously, and that a significant difference of responsiveness to abused drugs was indicated between these two lines. It is necessary to consider the alcohol preference when investigating the interaction of alcohol and/or other abused drugs.