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

恢复因灭绝或可用药物而抑制的药物维持行为

• 批准号: 7918899
• 负责人: BRETT C GINSBURG
• 金额: $ 19.85万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7918899
• 关键词: Abstinence; Adaptive Behaviors; Address; Alcohol consumption; Alcoholism; Animal Model; Animals; Anterior; Area; Behavior; Behavioral; Biology; Brain; Brain region; Characteristics; Dorsal; Drug Addiction; Drug usage; Environment; Ethanol; Event; Exposure to; Extinction (Psychology); Food; High Prevalence; Hippocampus (Brain); Human; Individual; Intravenous; Learning; Length; Life; Methods; Metric; Modeling; Neurobiology; Oral; Patient Self-Report; Pharmaceutical Preparations; Preparation; Procedures; Process; Psychological reinforcement; Public Health; Rattus; Recovery; Relapse; Research; Resistance; Route; Schedule; Self Administration; Self-Administered; Signal Transduction; Smoking; Stimulus; Stimulus Generalization; Testing; Time; Work; addiction; alcohol availability; alcohol reinforcement; cingulate cortex; craving; deprivation; disorder later incidence prevention; drinking; effective therapy; neurobiological mechanism; preclinical study; psychologic; public health relevance; reinforced behavior; response

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.

描述（由申请人提供）：只有通过了解复吸的行为和神经生物学机制，我们才能降低药物成瘾复吸的高患病率。为了研究这些机制，已经开发了复发的恢复模型，其中动物学会自我施用药物，然后对药物的反应被灭绝抑制：反应不再提供药物。一旦反应被抑制，暴露于药物、药物相关刺激或信号药物可用性的刺激导致对药物的反应恢复，尽管其持续缺失。这些相同的条件促进恢复成瘾者的复发。此外，在自我报告的渴望过程中激活的大脑区域也会减少恢复行为。然而，在人类中，禁欲很少是被迫的;成瘾者选择减少或停止使用药物，用其他适应性行为取代适应不良的药物使用。此外，在动物模型中，增加强制禁欲期会增加随后的复吸;而在人类中，更长的禁欲期会降低复发的可能性。因此，在行为和神经生物学机制方面可能存在根本差异，这些机制是药物自我给药行为的基础，药物自我给药行为已被消退抑制，而药物自我给药行为则被强化替代行为抑制。在这个建议中，（1）建立了条件，导致乙醇占主导地位或乙醇抑制的选择下，同时固定比例的时间表的食物和乙醇的强化。然后，在几种已知恢复抑制反应和促进复发的治疗后，比较抑制反应或选择抑制反应的恢复。(2)比较了几个脑区的可逆失活对抑制反应和选择抑制反应下的恢复反应的影响。(3)确定了每个程序中反应抑制期的长度对恢复反应的影响。最后，（4）在两种程序下，在乙醇自我给药或抑制乙醇自我给药30或60天后建立刺激泛化曲线。这种方法提供了有关行为的刺激控制的信息，可以帮助我们了解增加复发或促进康复的脆弱性的条件。这些研究将开始建立起选择决定因素与复职行为研究之间的整合关系。公共卫生相关性本项目通过加强替代行为而不是完全消除药物来抑制药物服用，从而增强了常用的复发行为动物模型。这更类似于戒毒者需要做出的决定。将测试大脑区域和禁欲期的影响。