The Role of AKAP 150 in the Nucleus Accumbens Shell in Cocaine Reinstatement

AKAP 150 在伏核壳中在可卡因恢复中的作用

基本信息

批准号：
8838499
负责人：
Leonardo Guercio
金额：
$ 4.31万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8838499
关键词：
A kinase anchoring protein AMPA Receptors Abstinence Age American Amino Acids Analgesics Animal Model Attenuated Behavior Binding Biological Markers Brain region Calcium Cells Clinical Research Co-Immunoprecipitations Cocaine Cocaine Abuse Cocaine Dependence Cocaine Users Cyclic AMP-Dependent Protein Kinases Dominant-Negative Mutation Dopamine Dopamine Agonists Dopamine Receptor Drug Addiction Drug Metabolic Detoxication Extinction (Psychology)FDA approved Food Hippocampus (Brain)Human Intervention Ion Channel Protein Learning Marijuana Mediating Memory Modeling Molecular Mutation Neurobiology Neuronal Plasticity Nucleus Accumbens Peptides Pharmaceutical Preparations Phosphorylation Play Proteins Psychological reinforcement Public Health Receptor Signaling Relapse Rodent Role Scaffolding Protein Self Administration Signal Transduction Specificity Surface Synapses Synaptic Cleft Synaptic plasticity Techniques Testing United States Virus Western Blotting Work base craving crosslink dopamine system dopamine transporter drug craving drug relapse improved indexing neuroadaptation neurochemistry novel overexpression postsynaptic pre-clinical protein expression public health relevance research study therapeutic development trafficking

项目摘要

DESCRIPTION (provided by applicant): Cocaine is the third most commonly abused illegal drug, after marijuana and prescription painkillers. In 2011, nearly 5 million Americans over the age of 12 abused cocaine. Following cocaine detoxification, the relapse rate among human addicts is discouragingly high, even after prolonged abstinence. Despite many years of pre- clinical and clinical research focused on improving our understanding of the neurochemical and neurobiological basis of cocaine addiction, there are no FDA-approved pharmacotherapeutic interventions for the treatment of cocaine abuse and relapse. Therefore, these studies will examine the role of a novel protein, AKAP150, in the reinstatement of cocaine-seeking behavior, an animal model of cocaine relapse. AKAP150 is known to interact with many signaling, receptor, and ion channel proteins that are involved in cocaine reinstatement; however, its role in cocaine seeking remains largely unexplored. These studies will help elucidate our understanding of the signaling cascades underlying cocaine relapse. Furthermore, these studies may help identify potential novel pharmacotherapeutic targets for the treatment of cocaine craving and relapse.

描述（由申请人提供）：可卡因是第三大最常滥用的非法药物，仅次于大麻和处方止痛药。 2011年，近500万12岁以上的美国人滥用可卡因。可卡因戒毒后，即使在长期戒断后，人类成瘾者的复吸率仍然高得令人沮丧。尽管多年来的临床前和临床研究致力于提高我们对可卡因成瘾的神经化学和神经生物学基础的理解，但目前还没有 FDA 批准的药物治疗干预措施用于治疗可卡因滥用和复发。因此，这些研究将探讨一种新型蛋白质 AKAP150 在恢复可卡因寻求行为（可卡因复发的动物模型）中的作用。已知 AKAP150 与许多信号、受体和离子通道蛋白相互作用，这些蛋白参与可卡因恢复；然而，其在寻求可卡因方面的作用在很大程度上仍未得到探索。这些研究将有助于阐明我们对可卡因复发背后的信号级联反应的理解。此外，这些研究可能有助于确定治疗可卡因渴望和复发的潜在新药物治疗靶点。