MOTIVATIONAL EFFECTS OF SELF-ADMINISTERED ETHANOL

拟议研究的总体目标是确定 调节酒精激发的行为。虽然酗酒是个问题 这受到了很多研究的关注，酒精的有效动物模型 解决这一问题的消费不足。拟议的研究 通过使用一种新的模型来克服这一点，该模型结合了蔗糖- 替代程序，以诱导高剂量的自我注射乙醇， 有一个跑道范例，允许评估动机 在未服用药物、未被剥夺权利的动物体内摄入乙醇。一系列 建议进行实验，以调查推定的 酒精刺激行为中的多巴胺奖赏系统，以及 苯二氮类药物系统在乙醇诱导的抗焦虑中的作用 效果。具体地说，将训练老鼠横穿直臂 用于口服乙醇/蔗糖溶液的跑道 增加乙醇浓度，降低蔗糖浓度。 已经证明(见初步数据)这一点 方法可以导致大量的乙醇消耗和可靠的操作 跑道回应。一次衡量业绩和消耗量的基线 是稳定的，跑道行为和乙醇摄入量的变化将是 多巴胺和苯二氮卓类受体预处理后的检查 对抗者。此外，这些药物的颅内输注将是 被用来试图定位大脑中有助于 自我给药乙醇的激励和强化作用。

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.