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（短期访问，ShA）可卡因自我管理经验 不会产生与成瘾相关的大脑和行为的变化。 成瘾模型涉及长时间访问程序（LgA，6 小时以上/天），这大大增加了 LgA 的摄入量会产生许多类似成瘾的行为，以及 然而，除了可卡因的使用量之外，ShA 还没有观察到大脑的变化。 使用的时间模式（间歇性如何）对于产生类似成瘾的效果也很重要 Zimmer 等人（2013）开发了一种间歇性行为。 访问自我管理程序（IntA）以更好地模拟可卡因的间歇模式 他发现，尽管吸毒总量少得多，但吸毒的动机仍然存在。 具有 IntA 经历的大鼠中的可卡因含量高于具有 LgA 经历的大鼠。 由此，我们发现 IntA 产生了强大的激励敏感性，如 可卡因需求逐步增加（基于行为经济指标） 相关的摄入量增加，以及可卡因寻求行为的非常强劲的恢复—— 尽管消耗的药物比 LgA 条件下少得多，因此，我们的总体目标是直接。 比较和对比这两者的行为、心理和神经生物学影响 成瘾模型的总体目标是确定大脑和行为是否发生变化。 LgA 与 IntA 产生的体验只是量上的不同，或者说，是否有质上的不同 这些信息对于做出有关结果的明智决策至关重要。 用于成瘾临床前研究的动物模型，并且对于确定 治疗学发展的方向。