MOTIVATIONAL EFFECTS OF SELF-ADMINISTERED ETHANOL

拟议研究的总体目标是确定 介导乙醇动机行为。虽然酗酒是一个问题 受到了很多研究的关注，有效的酒精动物模型， 缺乏解决这一问题的消费。 拟议研究 通过使用一种新的模型克服了这一点，该模型结合了蔗糖， 替代程序以诱导高剂量自我施用乙醇， 用跑道范例来评估动机， 消耗乙醇在unrugged非剥夺动物。一系列 实验提出了调查参与的假定 多巴胺奖励系统在乙醇动机行为， 苯二氮卓类药物对乙醇诱导的抗焦虑作用的影响 方面的影响.具体来说，将训练大鼠穿过直臂 口服乙醇/蔗糖溶液的通道， 增加乙醇浓度和降低蔗糖浓度。 已经证明（见初步数据）， 这种方法可以导致大量的乙醇消耗和可靠的操作 跑道收到性能和消耗的一次基线测量 稳定，跑道行为和乙醇摄入量的变化将是 用多巴胺和苯二氮卓受体预处理后检查 对手。此外，这些药物的颅内输注将 试图定位大脑部位， 自我管理的乙醇的激励和强化效果。

The overall objective of the proposed research is to determine the mediate ethanol-motivated behaviors. While alcohol abuse is a problem that receives much research attention, valid animal models of alcohol consumption that address this problem are lacking. The proposed research overcomes this with the use of a novel model that combines a sucrose- substitution procedure to induce high doses of self-administered ethanol, with a runway paradigm that allows for the assessment of motivation to consume ethanol in undrugged non-deprived animals. A series of experiments are proposed to investigate the involvement of the putative dopamine reward system in ethanol-motivated behavior, and the contribution of benzodiazepine systems to ethanol-induced anxiolytic effects. Specifically, rats will be trained to traverse a straight-arm runway for oral access to ethanol/sucrose solutions with progressively increasing ethanol concentrations and decreasing sucrose concentrations. It has already been demonstrated (see Preliminary Data) that this approach can lead to significant ethanol consumption and reliable operant runway responding. Once baseline measures of performance and consumption are stable, changes in runway behavior and ethanol intake will be examined following pretreatment with dopamine and benzodiazepine receptor antagonists. Additionally, intracranial infusions of these drugs will be employed in an attempt to localize the brain sites contributing to motivational and reinforcing effects of self-administered ethanol.