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Translational Neuropsychopharmacology Research of Nicotine Addiction

尼古丁成瘾的转化神经精神药理学研究

基本信息

批准号：
9753199
负责人：
Brett Froeliger
金额：
$ 29.28万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
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：
2015-09-15 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753199
关键词：
Abstinence Acetylcysteine Adjuvant Analgesic Amygdaloid structure Animal Model Animals Attenuated Behavior Behavioral Brain Brain Diseases Brain region Cessation of life Chemosensitization Chronic Clinical Clinical Research Cocaine Corpus striatum structure Cues Cysteine Data Dendritic Spines Equilibrium Foundations Functional Magnetic Resonance Imaging Glutamates Goals Human Individual Laboratories Measures Mediating Modeling Moods Morphology Motivation Negative Reinforcements Neurobiology Neurocognition Neurocognitive Neurophysiology - biologic function Neurosciences Nicotine Nicotine Dependence Nicotine Withdrawal Nucleus Accumbens Outcome Participant Pathway interactions Patient Self-Report Pharmaceutical Preparations Pharmacotherapy Placebos Pre-Clinical Model Prefrontal Cortex Process Prodrugs Psychological reinforcement Randomized Rattus Regulation Relapse Research Rest Rewards Self Administration Self-control as a personality trait Severities Smoker Smoking Smoking Behavior Synapses Synaptic plasticity Therapeutic Translational Research Translations Withdrawal Withdrawal Symptom addiction analog clinically relevant craving cue reactivity design disorder later incidence prevention executive function functional MRI scan human model insight interest negative affect neural circuit neural network neuromechanism neuropsychopharmacology nicotine replacement nicotine seeking behavior novel open label optogenetics pre-clinical preclinical study premature prevent promoter public health relevance response reward processing smoking abstinence smoking cessation smoking relapse transmission process treatment effect treatment group varenicline

项目摘要

DESCRIPTION (provided by applicant): Nicotine addiction is a manifold process that involves dysregulated executive control, reward processing and negative affect. Preclinical models reveal that self-administration of nicotine produces an imbalance in corticostriatal glutamate transmission that mediates cue-induced reinstatement to nicotine seeking. Prior research suggests that N-acetylcysteine (NAC), a modified cysteine chain that regulates glial glutamate and normalizes cocaine-induced synaptic plasticity, may attenuate perceived smoking reward and smoking behavior. Crucially however, our preclinical data suggests NAC may be most effective under conditions of abstinence as a relapse prevention aid. Thus, pairing a smoking cessation medication (Varenicline: VRN) that promotes abstinence, with a relapse prevention aid (NAC), may produce greater cessation outcomes than either treatment alone. The overarching goal of this proposal is to use clinical and preclinical neuroscience to investigate limbic-striatal and corticostriatal circuits involved in nicotine addiction and determine the valueof VRN+NAC for normalizing circuitry function and treating nicotine addiction. Smokers interested in quitting will be randomized to one of four placebo (PBO) controlled conditions to examine the individual and combined effects of VRN and NAC over 4-weeks. Following 1-week of treatment, participants will be contingently reinforced for 3 days of smoking abstinence and undergo an fMRI scan. Participants will be followed over the next 3-weeks of treatment and clinically relevant behaviors will be assessed. Relations between fMRI measures and clinical variable will be explored. In our analog preclinical studies that use the same treatment groups as the clinical studies, we will employ an optogenetic strategy to examine the efficacy of VRN+NAC at inhibiting synaptic plasticity in prelimbic (PL) and basolateral amygdala (BLA) inputs to the nucleus accumbens produced during cue-induced nicotine seeking.