Involvement of the rat infralimbic cortex and dorsolateral striatum in the facili

描述(申请人提供)：在成瘾中，吸毒和与吸毒相关的行为变得僵化，难以改变。虽然支持成瘾的药物的药理作用得到了很好的描述，但这些药物如何与大脑中的学习系统相互作用以加强吸毒行为是一个悬而未决的问题。更好地了解成瘾药物是如何影响自然学习和记忆系统的，对于我们治疗和预防药物成瘾的能力至关重要。拟议的研究重点是成瘾药物直接作用于学习系统以促进习惯学习的能力，以及确定可卡因在大脑中促进习惯学习的位置。具体目标#1将测试训练后注射可卡因促进大鼠习惯学习的能力。通过比较训练后注射生理盐水的行为与训练后注射可卡因的行为，将表征可卡因在记忆巩固期间通过行动促进习惯性反应的能力。然后，具体目标2将确定大脑中支持自然习惯学习的区域是否需要可卡因促进习惯学习的能力。训练前，将使用下缘皮质和背外侧纹状体(自然习惯学习的两个关键区域)的损伤来测试这两个结构是否都是可卡因促进成瘾所必需的。最后，具体目标#3将测试在记忆巩固过程中，下缘皮质和背外侧纹状体的可逆失活是否可以阻断可卡因促进习惯学习的能力。 与公共卫生相关：吸毒成瘾对受影响的个人和整个社会都有很高的代价。更好地了解成瘾药物影响学习和记忆的机制将为治疗和预防药物成瘾提供新的靶点。该项目的目标是1)表明可卡因可以直接作用于大脑中的习惯学习系统，以促进恰好发生在注射可卡因时的行为的习惯学习；2)识别大脑中哪些区域需要通过可卡因促进习惯学习；3)证明可卡因在记忆巩固期间在这些大脑区域发挥作用，以促进习惯学习。

DESCRIPTION (provided by applicant): In addiction, drug taking and behaviors associated with drug taking become rigid and difficult to modify. While the pharmacological actions of drugs that support addiction are well characterized, how these drugs interact with learning systems in the brain to reinforce drug taking behaviors is an open question. A better understanding of how addictive drugs co-opt natural learning and memory systems is critical for our ability to treat and prevent drug addiction. The proposed research focuses on the ability of addictive drugs to act directly on learning systems to facilitate the learning of habits, and on identifying the locations in the brain where cocaine acts to facilitate habit learning. Specific Aim #1 will test the ability of post-training injections of cocaine to facilitate habit learning in rats. By comparing behaviors paired with post-training saline injections to behaviors paired with post-training cocaine injections, the ability of cocaine to facilitate habitual responding by acting during memory consolidation will be characterized. Specific Aim #2 will then determine if areas in the brain that support the learning of natural habits are required for the ability of cocaine to facilitate habit learning. Pre-training lesions of the infralimbic cortex and the dorsolateral striatum (two critical regions for natural habit learning) will be used to test if both of these structures are required for habit facilitation by cocaine. Finally, Specific Aim #3 will test if reversible inactivation of the infralimbic cortex and dorsolateral striatum during memory consolidation can block the ability of cocaine to facilitate habit learning. PUBLIC HEALTH RELEVANCE: Drug addiction has high costs, both to affected individuals and to society as a whole. A better understanding of the mechanisms by which addictive drugs are able to influence learning and memory will provide novel targets for the treatment and prevention of drug addiction. The goals of this project are to 1) show that cocaine can act directly on habit learning systems in the brain to facilitate habit learning for behaviors that happen to occur close in time to when cocaine in administered, 2) to identify the areas of the brain which are required for the facilitation of habit learning by cocaine, and 3) to demonstrate that cocaine acts in these brain regions during memory consolidation to facilitate habit learning.