Infralimbic Regulation of Memory Consolidation of Extinction of Cocaine-seeking

描述（由申请人提供）：可卡因成瘾是困扰美国的一个严重问题，治疗仍然不完善。虽然大鼠可卡因自我给药和恢复的研究提供了很多关于可卡因成瘾的知识，但相对较少的研究探讨了大鼠自我给药行为的消退。尽管如此，可卡因自我给药的消失为减少可卡因使用复发的努力提供了一个主要的潜在药物靶点。因此，长期的目标，拟议的工作是调查的神经生物学的消退可卡因自我管理，并确定是否可以调节边缘下皮层活动，以影响记忆巩固的消退训练。先前的研究结果，加上初步的数据，表明涉及边缘下皮层的电路调节记忆巩固的可卡因自我管理的灭绝。所提出的实验将使用雄性Sprague-Dawley大鼠，其将经历可卡因自我给药，然后灭绝。大鼠将在消退训练的第1-5天的消退期后立即接受显微注射。具体目标#1将研究消退训练后边缘下皮层的失活如何影响消退训练的保持。具体目标#2将研究在消退训练后立即阻断边缘下皮层中的β 2-肾上腺素能受体是否会损害该训练的记忆巩固。具体目标#3将检查在消退训练期后立即激活下边缘皮层中的β 2-肾上腺素能受体是否增强该训练的记忆巩固。总之，这些实验将提供重要的新信息的电路基础的学习和记忆的消退可卡因自我管理，以及如何2-肾上腺素能受体阻滞剂和激活的边缘下皮层调制记忆巩固的消退训练。可卡因成瘾仍然是一个严重的问题，在很大程度上是由于治疗后复发率高。这项拟议中的研究将调查大鼠可卡因自我给药消退的神经生物学。这项研究将对公共卫生产生重大影响，因为灭绝过程是治疗药物成瘾的潜在药物靶点。

DESCRIPTION (provided by applicant): Cocaine addiction is a serious problem afflicting the United States, and treatment remains imperfect. Although the study of cocaine self-administration and reinstatement in rats has provided much knowledge of cocaine addiction, relatively few studies have explored the extinction of self-administration behavior in rats. Nonetheless, the extinction of cocaine self- administration provides a major potential pharmacotherapeutic target in the effort to reduce relapse to cocaine use. Therefore, the long-term objective of the proposed work is to investigate the neurobiology of extinction of cocaine self-administration and determine whether infralimbic cortical activity can be modulated to influence memory consolidation of extinction training. Previous findings, together with preliminary data, suggest that a circuit involving the infralimbic cortex regulates the memory consolidation of extinction of cocaine self-administration. The proposed experiments will use male Sprague-Dawley rats that will undergo cocaine self- administration followed by extinction. Rats will receive microinjections immediately AFTER extinction sessions on days 1-5 of extinction training. Specific Aim #1 will examine how inactivation of the infralimbic cortex immediately after extinction training sessions influences the retention of the extinction training. Specific Aim #2 will investigate whether blockade of 2- adrenergic receptors in the infralimbic cortex immediately after extinction training sessions impairs memory consolidation of that training. Specific Aim #3 will examine whether activation of 2-adrenergic receptors in the infralimbic cortex immediately after extinction training sessions enhances memory consolidation of that training. Together, these experiments will provide important new information on the circuitry underlying the learning and memory of extinction of cocaine self-administration and how 2-adrenergic receptor blockade and activation in the infralimbic cortex modulate memory consolidation of extinction training. Cocaine addiction remains a significant problem, in large part due to the high rate of relapse following treatment. The proposed research will investigate the neurobiology of the extinction of cocaine self-administration in rats. This research will have a significant impact on public health as the extinction process is a potential pharmacotherapeutic target in the treatment of drug addiction.