Infralimbic Regulation of Memory Consolidation of Extinction of Cocaine-seeking

描述(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。虽然可卡因在大鼠体内的自我给药和恢复的研究已经为可卡因成瘾提供了许多知识，但相对较少的研究探索了大鼠自我给药行为的消亡。尽管如此，在努力减少对可卡因的复吸方面，可卡因自我给药的消失提供了一个主要的潜在药物治疗目标。因此，这项拟议工作的长期目标是研究可卡因自我给药消退的神经生物学，并确定是否可以调节边缘下皮质活动来影响消退训练的记忆巩固。以前的发现和初步数据表明，涉及下缘皮质的回路调节可卡因自我给药消失的记忆巩固。拟议的实验将使用雄性Spraogue-Dawley大鼠，这些大鼠将经历可卡因自我给药，然后灭绝。大鼠将在灭绝训练的第1-5天的灭绝会议后立即接受微量注射。具体目标#1将检查消退训练后立即失活的下缘皮质如何影响消退训练的保留。具体目标#2将调查在消亡训练后立即阻断下缘皮质中的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将检查消失式训练后立即激活下缘皮质中的2-肾上腺素能受体是否增强了训练的记忆巩固。总之，这些实验将提供重要的新信息，涉及可卡因自我给药学习和记忆消退的潜在回路，以及边缘皮质下皮质2-肾上腺素能受体阻断和激活如何调节消退训练的记忆巩固。可卡因成瘾仍然是一个严重的问题，这在很大程度上是由于治疗后的高复发率。这项拟议的研究将调查大鼠体内可卡因自我给药消失的神经生物学。这项研究将对公众健康产生重大影响，因为消退过程是治疗药物成瘾的潜在药物治疗靶点。

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.