Cocaine, Electroconvulsive Seizure and Neural Plasticity

可卡因、电惊厥和神经可塑性

• 批准号: 7296126
• 负责人: Barbara A Sorg
• 金额: $ 17.82万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7296126
• 关键词: Abbreviations; Anesthesia procedures; Animals; Behavior; Brain; Brain region; Brain-Derived Neurotrophic Factor; Cocaine; Cocaine Dependence; Condition; Depth; Disruption; Dose; Drug Addiction; Effectiveness; Electroconvulsive Shock; Electroconvulsive Therapy; Electroencephalography; Extinction (Psychology); Future; Goals; Growth Factor; Hour; Human; Individual; Lead; Learning; Long-Term Potentiation; Measures; Medial; Memory; Mental Depression; Nature; Neurobiology; Neuronal Plasticity; Numbers; Pattern; Pharmaceutical Preparations; Phase; Physiologic pulse; Prefrontal Cortex; Proteins; Pulse taking; Rattus; Relapse; Relative (related person); Research Personnel; Role; Seizures; Side; Testing; Thinking; Time; Ventral Tegmental Area; attenuation; craving; day; drug seeking behavior; interest; novel; preference; prevent; programs; restoration; therapy development; Abbreviations; Anesthesia procedures; Animals; Behavior; Brain; Brain region; Brain-Derived Neurotrophic Factor; Cocaine; Cocaine Dependence; Condition; Depth; Disruption; Dose; Drug Addiction; Effectiveness; Electroconvulsive Shock; Electroconvulsive Therapy; Electroencephalography; Extinction (Psychology); Future; Goals; Growth Factor; Hour; Human; Individual; Lead; Learning; Long-Term Potentiation; Measures; Medial; Memory; Mental Depression; Nature; Neurobiology; Neuronal Plasticity; Numbers; Pattern; Pharmaceutical Preparations; Phase; Physiologic pulse; Prefrontal Cortex; Proteins; Pulse taking; Rattus; Relapse; Relative (related person); Research Personnel; Role; Seizures; Side; Testing; Thinking; Time; Ventral Tegmental Area; attenuation; craving; day; drug seeking behavior; interest; novel; preference; prevent; programs; restoration; therapy development

DESCRIPTION (provided by applicant): We speculate that the long-lasting nature of cocaine and other drug addiction may be due to drug-induced changes that ultimately produce a loss of plasticity in specific brain regions involved with craving and relapse. A novel conceptualization for the treatment of cocaine addiction is that restoration of neural plasticity during the period when the individual is learning to stay away from drugs (the extinction phase) may prevent relapse to drug-seeking or drug-taking behavior. The proposed studies focus on providing a new framework for suppressing relapse by manipulating the extinction period of drug-seeking behavior. Thus, we may take advantage of a critical window during which learning to avoid drug seeking/taking may be enhanced by simultaneous induction of neural plasticity. Electroconvulsive therapy (ECT) or seizure (ECS) is now viewed as successful in treating severe depression because of its ability to increase neural plasticity in the brain. Key molecules thought to be involved in ECS-induced plasticity are growth factors. Because extinction is new learning, alteration of growth factors during the extinction phase of cocaine-induced conditioned place preference (CPP) may reduce the reinstatement of drug-seeking behavior in rats. Our studies show that ECS given during the extinction phase suppresses reinstatement of cocaine-primed CPP compared with controls. The same ECS treatments delivered prior to the extinction phase did not alter reinstatement. The primary goal of these studies is to optimize the parameters of ECS treatment to produce maximal suppression of cocaine-primed reinstatement. The proposed studies center on the main hypothesis that ECS treatment is most effective in suppressing cocaine-primed reinstatement when given during the extinction phase. Specific Aim 1 will determine the effects of seizure duration and number of days of ECS treatment on reinstatement of cocaine-primed CPP. Seizure duration will be altered by changing the pulse dose and duration of ECS and depth of anesthesia during ECS treatments. Specific Aim 2 will optimize the timing of ECS treatment for its ability to suppress reinstatement of cocaine-primed CPP. The timing of ECS will be shifted to before, during or after the extinction phase. This Aim will also test ECS timing (in hours) relative to extinction to determine if the timing of ECS is important for the suppression of reinstatement. Our studies indicate that ECT in humans may be an option for some cases of cocaine addiction, as it is for severe depression in humans. However, our long term interest is to understand the critical neurobiological consequences of ECS that could lead to treatment for cocaine addiction.

描述（由申请人提供）：我们推测可卡因和其他药物成瘾的持久性质可能是由于药物诱导的变化所致，这些变化最终导致与渴望和复发有关的特定大脑区域的可塑性丧失。可卡因成瘾治疗的一种新颖的概念化是，在个人正在学习远离药物（灭绝阶段）的时期，神经可塑性的恢复可能会阻止人们复发到寻求吸毒或吸毒行为。拟议的研究着重于通过操纵寻求毒品行为的灭绝时期提供一个新的框架来抑制复发。因此，我们可以利用一个关键窗口，在此期间，通过同时诱导神经可塑性，可以增强学习避免吸毒/服用药物的临界窗口。现在，电抽取疗法（ECT）或癫痫发作（EC）被视为成功治疗严重的抑郁症，因为它具有增加大脑中神经可塑性的能力。被认为与EC诱导的可塑性有关的关键分子是生长因素。由于灭绝是新的学习，因此在可卡因诱导的条件偏好（CPP）的灭绝阶段改变生长因子的改变可能会减少大鼠毒品寻求毒品行为的恢复。我们的研究表明，与对照组相比，在灭绝阶段给出的EC抑制可卡因剂的CPP的恢复。在灭绝阶段之前提供的相同的EC处理并没有改变恢复原状。这些研究的主要目的是优化ECS处理的参数，以最大程度地抑制可卡因培养的恢复原状。拟议的研究集中在主要假设中，即ECS治疗在灭绝阶段给出时最有效地抑制可卡因剂的恢复。具体的目标1将确定癫痫发作持续时间和EC治疗天数对可卡因蛋白CPP的恢复的影响。癫痫发作持续时间将通过改变EC治疗期间EC的脉搏剂量和持续时间以及麻醉深度来改变。特定的目标2将优化ECS治疗的时间，以抑制可卡因培养的CPP的能力。 EC的时间将转移到灭绝阶段之前，期间或之后。该目标还将测试EC的时间（以小时）相对于灭绝，以确定EC的时机对于抑制恢复是否重要。我们的研究表明，在某些可卡因成瘾的情况下，人类的ECT可能是一种选择，因为它是针对人类严重抑郁症的选择。但是，我们的长期兴趣是了解EC的关键神经生物学后果，这可能导致可卡因成瘾治疗。