Methamphetamine psychosis: A model in man and mouse

甲基苯丙胺精神病：人和小鼠的模型

基本信息

批准号：
7551887
负责人：
DANIEL A ALICATA
金额：
$ 57.02万
依托单位：
UNIVERSITY OF HAWAII AT MANOA
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7551887
关键词：
18 year old Abstinence Acute Adolescent Adrenal Glands Adult Affect Age Amygdaloid structure Animal Experiments Anterior Autopsy Award Basal Ganglia Behavior Bicycling Brain Brain region California Cerebrum Child Choline Chronic Clinical Clinical assessments Cognitive deficits Collaborations Complement Condition Consultations Control Groups Corpus striatum structure DNA DOPA decarboxylase DSM-IV Data Delusions Diagnostic Diffusion Disease Doctor of Medicine Dose Drug abuse Drug user Emotional Evaluation FOS Family Genes Female Functional Magnetic Resonance Imaging Funding Future Gender Genes Genetic Risk Gliosis Goals Grant Hallucinations Hawaii Hippocampus (Brain)Human Hydrocortisone Hypothalamic structure Ice Image Imaging Device Imaging Techniques Imaging technology Impaired cognition Intention Iowa Laboratories Lateral Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Maps Measurable Measures Mediating Membrane Memory Memory impairment Metabolic Metabolism Methamphetamine Methodology Methods Modeling Mus N-acetylaspartate Nerve Neurologic Examination Neurons Neurotransmitters Participant Patients Pattern Peptides Pharmaceutical Preparations Physical assessment Pituitary Gland Population Positron-Emission Tomography Prefrontal Cortex Prevalence Production Property Protocols documentation Protons Psychosocial Stress Psychotic Disorders Public Health Range Rate Recording of previous events Recruitment Activity Reporting Research Ethics Committees Resolution Rewards Rodent Saliva Salivary Sampling Schizophrenia Screening procedure Series Severities Societies Staging Stress Stress Tests Structure Study Subject Symptoms System Technology Testing Thinking Time Tissues Toxic effect Trier Social Stress Test Universities Variant Water Work addiction base biological adaptation to stress brain morphology cingulate cortex clinically relevant cognitive change cognitive function cohort computerized dopamine transporter dopaminergic neuron drug abstinence drug mechanism drug of abuse expectation experience fight against frontal lobe healthy aging human study human subject hypothalamic-pituitary-adrenal axis insight interest male man methamphetamine exposure mouse model myoinositol neuronal cell body neuropathology neuropsychological neurotoxic psychologic psychological stressor psychosocial relating to nervous system response social stressor vesicular monoamine transporter water diffusion white matter

项目摘要

Drug abuse is an important public health problem in all human societies. One fast spreading drug has been methamphetamine, known as "ice" in its crystal form. This is an increasingly popular and addictive drug of abuse among adolescents. Exposure is often associated with symptoms of psychosis, indistinguishable from schizophrenia, as well as cognitive impairment. Vulnerable drug users experience persistent psychosis and neuropsychological deficits even after long periods of abstinence. Increased understanding of this drug's mechanism of action may be useful in the public fight against its damaging effects, while also providing insight into the mechanisms of psychosis. We will establish a cohort of 100 adolescent subjects with a history of methamphetamine exposure and a second group of 50 age- and gender-matched healthy adolescents. Our Specific Aims examine the following working hypotheses: 1) that clinical assessment will be able to characterize the variation of intensity and duration of psychotic symptoms with the expectation that the severity of these symptoms will not correlate with cognitive changes, especially memory deficits within our adolescent sample population; 2) that the volumes and metabolism of frontal cortex, striatum, anterior cingulate cortex, and hippocampus, as measured with 3-Tesla MR imaging tools, will be significantly reduced in methamphetamine-exposed adolescents; 3) that strong disturbance of the HPA axis response to psychosocial stress is significantly correlated with the severity of psychotic symptoms, whereas the correlation with cognitive impairment especially memory deficits, will be less significant; 4) that morphological alterations in the mouse cortex striatum and hippocampus in response to methamphetamine are similar to those in humans. From our proposed mouse studies we expect to develop a comprehensive understanding of methamphetamine-induced brain changes because such an understanding cannot readily be obtained from humans. In this way, we utilize the mouse model to investigate functional, microstructural and histochemical effects on the brain under well controlled experimental conditions. We believe these studies will contribute to the overall aims of this award by further delineating how stressors affect emotional and cognitive functions.

药物滥用是所有人类社会的重要公共卫生问题。一种快速扩散的药物是甲基苯丙胺，其晶体形式称为“冰”。这是青少年越来越受欢迎且令人上瘾的虐待药物。暴露通常与精神病症状有关，与精神分裂症没有区别以及认知障碍。脆弱的吸毒者即使经过长时间的禁欲，也会经历持续的精神病和神经心理学缺陷。对这种药物作用机制的了解增加可能对公众对抗其破坏性影响有用，同时还提供了对精神病机制的见解。我们将建立100名青少年受试者的队列，并具有甲基苯丙胺暴露史以及第二组50岁和性别匹配的健康青少年。我们的具体目的检查了以下工作假设：1）临床评估将能够表征精神病症状的强度和持续时间的变化，并期望这些症状的严重程度与认知变化无关，尤其是我们的青少年样本中的记忆缺陷； 2）那用3- tesla MR成像工具测量的额叶皮质，纹状体，前扣带回皮层和海马的体积和代谢将在甲基苯丙胺暴露的青少年中显着降低； 3）HPA轴对社会心理压力的反应的强烈干扰与精神病症状的严重程度显着相关，而与认知障碍（尤其是记忆缺陷）的相关性将不那么重要； 4）小鼠皮质纹状体和海马的形态改变对甲基苯丙胺的反应与人类相似。从我们提出的小鼠研究中，我们期望对甲基苯丙胺引起的大脑变化有全面的理解，因为这种理解无法轻易从人类那里获得。这样，我们利用鼠标模型来研究功能，微结构和组织化学在良好控制的实验条件下对大脑的影响。我们认为，这些研究将通过进一步描述压力源如何影响情绪和认知功能来促进该奖项的总体目标。