Animal Models of Addiction

成瘾动物模型

• 批准号: 9524030
• 负责人: Terry E. Robinson
• 金额: $ 44.91万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9524030
• 关键词: AMPA Receptors; Animal Model; Behavior; Behavioral; Biochemical; Biological; Brain; Calcium; Cocaine; Cocaine Dependence; Consumption; Corpus striatum structure; Cues; Data; Development; Dialysis procedure; Dopamine; Drug usage; Electrophysiology (science); Excision; Female; Food; Glutamates; Goals; Hyperactive behavior; Incentives; Intake; Kava; Literature; Mediating; Methods; Modeling; Motivation; Neurobiology; Nucleus Accumbens; Outcome; Pattern; Permeability; Pharmaceutical Preparations; Preparation; Procedures; Psychology; Rattus; Reporting; Rodent; Sampling; Self Administration; System; Testing; Therapeutic; Time; Withdrawal; Wolves; addiction; base; behavior change; behavioral economics; brain behavior; cocaine use; craving; data integration; dopamine system; drug abuse prevention; drug seeking behavior; economic indicator; experience; experimental study; indexing; male; neuroadaptation; neurotransmission; preclinical study; psychologic; relating to nervous system; response; therapeutic development; transmission process

Abstract: It is generally accepted that limited (Short Access, ShA) cocaine self-administration experience does not produce changes in brain and behavior associated with addiction. The most widely used models of addiction involve Long Access procedures (LgA, 6hrs+/day), which greatly increase the amount of drug consumption. LgA produces a number of addiction-like behaviors, and changes in brain, not seen with ShA. However, in addition to the amount of cocaine use, the temporal pattern of use – how intermittent it is – is also important in producing addiction-like behavior and associated neuroadaptations. Zimmer et al. (2013) developed an intermittent access self-administration procedure (IntA) to better model the intermittent patterns of cocaine use seen in addicts. He found that, despite much less total drug consumption, motivation for cocaine was higher in rats with prior IntA experience than those with LgA experience. Consistent with this, we found that IntA produces robust incentive-sensitization, as indicated by a progressive increase in cocaine demand (based on behavioral economic indicators), an associated escalation of intake, and very robust reinstatement of cocaine seeking behavior – despite consuming much less drug than under LgA conditions. Thus, our Overall Aim is to directly compare and contrast the behavioral, psychological and neurobiological effects of these two models of addiction. The overall goal is to determine whether the changes in brain and behavior produced by LgA vs. IntA experience only differ quantitatively, or, whether there are qualitative differences in outcomes. This information will be critical in making informed decisions about the animal model to use in preclinical studies of addiction, and will also be important in determining directions in the development of therapeutics.

抽象的： 人们普遍认为，有限的（短访问，sha）可卡因自我管理经验 不会产生与成瘾有关的大脑和行为的变化。最广泛使用的 成瘾模型涉及长期访问程序（LGA，6小时+/天），大大增加 吸毒的量。 LGA产生许多类似成瘾的行为，并且 大脑的变化，没有SHA。但是，除了可卡因的使用量之外， 暂时的使用模式 - 间歇性的方式 - 在产生类似成瘾的情况下也很重要 行为和相关的神经照射。 Zimmer等。 （2013）发展了 访问自我管理程序（INTA），以更好地建模可卡因的间歇性模式 在成瘾者中看到的使用。他发现，目的地的总毒品消耗要少得多 与LGA经验的大鼠相比，在先前的内部经验的大鼠中，可卡因的可卡因高。持续的 因此，我们发现INTA产生强大的激励敏感性，如A所示 可卡因需求的逐步增加（基于行为经济指标），这是一个 相关的摄入量升级，以及对可卡因寻求行为的非常强大的恢复 - 尽管在LGA条件下的药物要少得多。那是我们的总体目标是直接 比较和对比这两个的行为，心理和神经生物学效应 成瘾模型。总体目标是确定大脑和行为的变化是否 由LGA与Inta的经验仅不同，或者是否有定性 结果的差异。这些信息对于做出有关明智的决定至关重要 在成瘾的临床前研究中使用的动物模型，并且在确定方面也很重要 疗法发展的方向。