Reinstatement of drug-maintained behavior suppressed by extinction or an availabl

描述(申请人提供)：只有通过了解复吸的行为和神经生物学机制，我们才能降低复吸的高流行率。为了研究这些机制，已经建立了复发的恢复模型，在该模型中，动物学习自我给药，然后对药物的反应被灭绝抑制：反应不再提供获得药物的途径。一旦反应被抑制，暴露在药物、药物相关刺激或药物可获得性信号的刺激下，会导致对药物的反应恢复，尽管药物仍然不存在。同样的情况也会促使戒毒者复发。此外，在自我报告的渴望过程中活跃的大脑区域的失活也会减少恢复行为。然而，在人类中，禁欲很少是强制的；吸毒者选择减少或停止使用药物，用其他适应行为取代不适应的药物使用。此外，在动物模型中，增加强制禁欲的时间会增加随后的恢复；但在人类中，更长的禁欲时间会降低复发的可能性。因此，在被灭绝抑制的药物自我给药行为和通过强化替代行为而被抑制的行为背后的行为和神经生物学机制可能存在根本的不同。在这一建议中，(1)建立了在食品和乙醇强化的同时固定比例计划下导致乙醇占优势或乙醇抑制的选择的条件。然后，在几种已知的恢复消退抑制的反应和加速复发的治疗之后，比较了恢复消退抑制的反应或选择抑制的反应。(2)比较了消退抑制反应和选择抑制反应下多个脑区的可逆失活对恢复反应的影响。(3)确定响应抑制周期的长度对每个程序中恢复响应的影响。最后，(4)在两种程序下，分别在30天或60天酒精自我给药或抑制乙醇自我给药后，建立刺激泛化曲线。这种方法提供了有关行为刺激控制的信息，并可以帮助我们了解增加复发或促进康复的易感性的条件。这些研究将开始建立选择决定因素和复职行为研究之间的综合关系。公共卫生相关性该项目通过加强另一种行为而不是完全戒除毒品来抑制吸毒，从而增强了一种常用的复发行为动物模型。这更类似于戒毒者康复所需的决定。将测试大脑区域和禁酒期的影响。

DESCRIPTION (provided by applicant): Only by understanding behavioral and neurobiological mechanisms that underlie relapse can we reduce the high prevalence of relapse to drug addiction. To study these mechanisms, the reinstatement model of relapse has been developed, where animals learn to self-administer a drug, and then responding for the drug is suppressed by extinction: responses no longer provide access to the drug. Once responding is suppressed, exposure to the drug, drug-associated stimuli, or stimuli signaling drug availability result in a resumption of responding for the drug, despite its continuing absence. These same conditions promote relapse in recovering addicts. Also, inactivating brain regions that are active during self-reported craving reduce reinstatement behavior. However, in humans, abstinence is rarely forced; addicts choose to reduce or stop drug use, replacing maladaptive drug use with other, adaptive behaviors. Additionally, in the animal model, increasing the period of forced abstinence increases subsequent reinstatement; yet in humans longer periods of abstinence reduce the likelihood of relapse. Thus there could be a fundamental difference in the behavioral and neurobiological mechanisms that underlie drug self-administration behavior that has been suppressed by extinction verses behavior suppressed by reinforcing an alternative behavior. In this proposal, (1) conditions are established that result in ethanol-predominant or ethanol-suppressed choices under a concurrent fixed-ratio schedule of food and ethanol reinforcement. Then, reinstatement of extinction-suppressed or choice-suppressed responding is compared following several treatments known to reinstate extinction-suppressed responding and precipitate relapse. (2) The impact of reversible inactivation of several brain regions on reinstatement responding under extinction-suppressed and choice-suppressed responding is compared. (3) The impact of the length of the period of response suppression on reinstatement responding in each procedure is determined. Finally, (4) stimulus generalization curves are established following 30 or 60 days of ethanol self-administration or suppressed ethanol-self-administration under both procedures. This method provides information about the stimulus control of a behavior and could help us understand conditions that increase vulnerability to relapse or promote recovery. These studies will begin to build an integrative relationship between studies on the determinates of choice and reinstatement behaviors. PUBLIC HEALTH RELEVANCE This project enhances a commonly used animal model of relapse behavior by suppressing drug taking by reinforcing an alternative behavior rather than removing drug altogether. This is more similar to the decisions required of recovering addicts. The influence of brain regions and abstinence period will be tested.