Yan Q S, Reith M E, Jobe P C, Dailey J W
Department of Basic Sciences, University of Illinois College of Medicine at Peoria 61656, USA.
Eur J Pharmacol. 1996 Apr 22;301(1-3):49-57. doi: 10.1016/0014-2999(96)00018-0.
The present study describes the effects of local perfusion with ethanol on extracellular dopamine and serotonin (5-hydroxytryptamine, 5-HT) concentrations in the ventral tegmental area. Various concentrations of ethanol in artificial cerebrospinal fluid (ACSF) (0.1-10%, v/v) were administered through a microdialysis probe into the ventral tegmental area of freely moving Sprague-Dawley rats. A significant and concentration-dependent increment in dialysate output of both dopamine and serotonin was observed after local infusion of ethanol. Perfusion with Ca(2+)-free medium or tetrodotoxin (1 microM in ACSF) produced a significant reduction in basal extracellular dopamine and serotonin concentration but failed to block dopamine or serotonin release produced by infusion of 10% ethanol. Perfusion with 100 mM K+ before and after infusion of 10% ethanol revealed that the second perfusion with high K+ solution still produced an increase in dopamine and serotonin concentration, similar in magnitude to the first response, indicating that perfusion with 10% ethanol did not cause irreversible damage to either dopamine cell bodies or serotonin terminals in the ventral tegmental area. These results suggest that dopamine and serotonin release from the ventral tegmental area produced by focal application of 10% ethanol is mediated, at least in part, by a non-exocytotic mechanism. Direct stimulation of the ventral tegmental area dopamine neurons by ethanol might be involved in the reinforcing properties of the drug.
本研究描述了乙醇局部灌注对腹侧被盖区细胞外多巴胺和5-羟色胺(5-HT)浓度的影响。通过微透析探针将不同浓度(0.1-10%,v/v)的乙醇人工脑脊液(ACSF)注入自由活动的Sprague-Dawley大鼠的腹侧被盖区。局部注入乙醇后,观察到多巴胺和5-羟色胺的透析液输出量显著增加,且呈浓度依赖性。用无钙培养基或河豚毒素(ACSF中1μM)灌注可使基础细胞外多巴胺和5-羟色胺浓度显著降低,但不能阻断注入10%乙醇所引起的多巴胺或5-羟色胺释放。在注入10%乙醇前后用100 mM K+灌注显示,第二次用高K+溶液灌注仍可使多巴胺和5-羟色胺浓度升高,幅度与第一次反应相似,这表明用10%乙醇灌注不会对腹侧被盖区的多巴胺细胞体或5-羟色胺终末造成不可逆损伤。这些结果表明,局部应用10%乙醇所引起的腹侧被盖区多巴胺和5-羟色胺释放至少部分是由非胞吐机制介导的。乙醇对腹侧被盖区多巴胺神经元的直接刺激可能与该药物的强化特性有关。