Animal Models of Addiction

摘要： 人们普遍认为，有限的（短期接触，ShA）可卡因自我管理经验 不会引起与成瘾相关的大脑和行为变化。最广泛使用的 成瘾模型涉及长期访问程序（LGA，6小时+/天），这大大增加了 毒品消费量。LgA产生许多成瘾样行为， 脑内变化，ShA未见。然而，除了可卡因的使用量， 使用的时间模式--它的间歇性--在产生类似成瘾的情况下也很重要 行为和相关的神经适应。Zimmer等人（2013）开发了一种间歇性 访问自我管理程序（IntA），以更好地模拟可卡因的间歇模式 在瘾君子中使用。他发现，尽管总的药物消费量少得多， 可卡因在有IntA经验的大鼠中高于有LgA经验的大鼠。一致 有了这个，我们发现IntA产生了强大的激励敏感化，如图所示。 可卡因需求逐步增加（根据行为经济指标）， 相关的摄入量增加，以及可卡因寻求行为的强烈恢复- 尽管消耗的药物比在LGA条件下少得多。因此，我们的总体目标是直接 比较和对比这两种行为，心理和神经生物学影响 成瘾的模型总体目标是确定大脑和行为的变化是否 由LgA与IntA经验产生的差异只是数量上的，或者，是否有质量上的差异， 结果的差异。这一信息对于作出有关 动物模型用于成瘾的临床前研究，也将是重要的， 治疗学的发展方向。

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.