COGNITIVE ASPECTS OF ADDICTION-RELATED BEHAVIOR

描述：(申请人摘要) 最近成像技术的进步已经开始表明，有几个 大脑部位，以前被证明与不同的记忆有关 系统在可卡因相关线索诱导的渴求过程中被激活 人类受试者。研究表明，边缘和皮质之间存在联系 结构在调节药物渴求中的作用并强调其可能的重要性 对吸毒成瘾的这一方面和其他方面的认知过程。这个 拟议的计划是使用神经系统的方法来检查 不同记忆系统与成瘾的关系 二阶静脉注射可卡因和可卡因的行为研究 大鼠体内注射吗啡。一种二阶递送药品时间表 衡量被认为与吸毒渴望和吸毒有关的行为。 提出了两个互为补充的项目。第一个项目将确定 来自不同记忆系统的信息如何调控成瘾相关 行为。将在吸食可卡因的过程中测量与成瘾相关的行为 服药一段时间后的维持和恢复(复发) 戒烟。双侧输注利多卡因和TTX将用于 暂时和可逆性地阻断神经元活动，以及 四大记忆系统内的特定部位(杏仁基底外侧核， 海马体、背侧纹状体和前额叶皮质)参与调节 将毒品寻觅和毒品消费行为进行比较。这个 该项目的完成可以确定功能机制和 认知和药物渴求、使用和复发的解剖学途径 连接在一起。在第二个项目中，老鼠将被维持在第二级 可卡因或吗啡的输送时间表及其在电池上的性能 认知任务的表现将与吸毒和吸毒的表现进行比较 盐水缠绕的大鼠。任务将包括以海马体为目标的任务， 基底外侧杏仁核、背侧纹状体和前额叶皮质记忆 功能。这些程序将隔离以下具体后果 持续给药不同于一般药理给药 药物对认知能力的影响。影响的一般性 与成瘾相关的行为对认知表现的影响可以通过以下方式确定 比较不同药物作用机制的不同。 该项目可能确定面临的独特认知挑战 吸毒成瘾者

DESCRIPTION: (Applicant's Abstract) Recent advances in imaging technology have begun to indicate that several brain sites, previously shown to be associated with different memory systems, are activated during craving induced by cocaine-associated cues in human subjects. Studies suggest a link between limbic and cortical structures in mediating drug craving and underscore the possible importance of cognitive processes for this and other aspects of drug addiction. The proposed plan is to use a neural systems approach to examine the relationships between different memory systems and addiction-related behavior studied with a second-order schedule of intravenous cocaine and morphine delivery in rats. A second-order schedule of drug delivery measures behaviors thought to be related to drug craving and to drug use. Two complementary projects are proposed. The first project will identify how information from different memory systems regulates addiction-related behavior. Addiction-related behavior will be measured during cocaine maintenance and reinstatement (relapse) that follow a period of drug withdrawal. Bilateral infusions of lidocaine and TTX will be used to temporarily and reversibly block neuronal activity, and the roles of specific sites within the four major memory systems (basolateral amygdala, hippocampus, dorsal striatum and prefrontal cortex) in regulating drug-seeking and drug-consummatory behavior will be compared. The completion of this project may identify the functional mechanisms and anatomical pathways by which cognition and drug craving, use and relapse are connected. In the second project, rats will be maintained on a second-order schedule of cocaine or morphine delivery and their performance on a battery of cognitive tasks will be compared to the performance of drug-yoked and saline-yoked rats. Tasks will include those that target hippocampal, basolateral amygdala, dorsal striatal and prefrontal cortex memory functions. These procedures will isolate the specific consequences of persistent drug self-administration from those of a general pharmacological effect of the drug on cognitive performance. The generality of the effects of addiction related behavior on cognitive performance can be determined by comparing different drugs of abuse which differ in mechanism of action. This project may identify the unique cognitive challenges that face a drug-addicted individual