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Animal Models of Addiction

成瘾动物模型

基本信息

批准号：
10307147
负责人：
Terry E. Robinson
金额：
$ 45.6万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/10307147
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 Hyperactivity 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 self-administration 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

项目摘要

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.

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