Shoemaker William J, Vavrousek-Jakuba Eva, Arons Cynthia D, Kwok Fung Cho
Department of Psychiatry, School of Medicine, University of Connecticut Health Center, Farmington Avenue, , Farmington, CT 06030, USA.
Behav Brain Res. 2002 Dec 2;137(1-2):139-48. doi: 10.1016/s0166-4328(02)00290-5.
Wistar male rats were microinfused bilaterally with 6-hydroxydopamine or vehicle into the ventral tegmental area. After recovery, ethanol drinking was established using a sucrose-fading paradigm, i.e. rats were given twice a day access to drinks containing increasing amounts of ethanol and decreasing amounts of sucrose. Mean daily intakes at each ethanol/sucrose concentration were similar irrespective of the level of dopamine depletion that, in some animals, reached 80-90%. The percentage of rats testing as ethanol preferers in a two-bottle choice test also appeared similar in both the lesioned and control groups. After completing the sucrose-fading protocol, all rats were switched to one access per day during which they were presented with a drink containing 10% ethanol with 5% sucrose. Naloxone administration (15 min before the daily access period) decreased ethanol beverage consumption by about 50%, irrespective of the level of dopamine depletion. Total daily water intake was not altered by naloxone. In a two-bottle choice situation, naloxone suppressed intake of an ethanol drink (10% ethanol/5% sucrose), but not the intake of 5% sucrose alone. Thus, a lesion of the dopaminergic cell bodies that results in extensive depletion of dopamine in mesolimbic target regions produced no measurable effect on intake of the sweetened ethanol drinks during the acquisition phase of the sucrose-fading paradigm. Furthermore, during the maintenance phase of drinking, the marked effect of naloxone in inhibiting ethanol beverage ingestion (but not water ingestion or sucrose alone solutions) occurred despite extensive loss of dopaminergic innervation to telencephalic target regions. A preliminary account of these experiments appeared in an abstract form and as an Internet publication. (Supported by NIAAA grants P50-03510 and T32-0720).
将6-羟基多巴胺或赋形剂双侧微量注入Wistar雄性大鼠的腹侧被盖区。恢复后，采用蔗糖递减模式建立乙醇饮用习惯，即每天给大鼠两次机会饮用含乙醇量增加而蔗糖量减少的饮料。无论多巴胺耗竭程度如何（在一些动物中，多巴胺耗竭达到80-90%），每种乙醇/蔗糖浓度下的平均每日摄入量相似。在双瓶选择试验中，测试为乙醇偏好者的大鼠百分比在损伤组和对照组中也似乎相似。完成蔗糖递减方案后，所有大鼠改为每天一次饮用机会，在此期间给它们提供含10%乙醇和5%蔗糖的饮料。给予纳洛酮（在每日饮用期前15分钟）可使乙醇饮料消耗量减少约50%，与多巴胺耗竭程度无关。纳洛酮未改变每日总饮水量。在双瓶选择情况下，纳洛酮抑制乙醇饮料（10%乙醇/5%蔗糖）的摄入，但不抑制单独5%蔗糖的摄入。因此，多巴胺能细胞体损伤导致中脑边缘靶区域多巴胺大量耗竭，在蔗糖递减模式的获取阶段，对甜味乙醇饮料的摄入没有产生可测量的影响。此外，在饮用维持阶段，尽管向端脑靶区域的多巴胺能神经支配大量丧失，但纳洛酮在抑制乙醇饮料摄入（但不抑制水摄入或单独蔗糖溶液摄入）方面仍有显著作用。这些实验的初步报告以摘要形式和网络出版物形式出现。（由美国国立酒精滥用与酒精中毒研究所资助，项目编号P50-03510和T32-0720）
