Adolescent Vulnerability to Psychostimulants: Effects of Sex and Food Restriction

青少年对精神兴奋剂的脆弱性：性和食物限制的影响

• 批准号: 7531349
• 负责人: NICOLE C BARBARICH-MARSTELLER
• 金额: $ 17.57万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-15 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7531349
• 关键词: Addictive Behavior; Address; Adolescence; Adolescent; Adult; Age; Anorexia; Award; Behavioral; Chronic; Clinical; Comorbidity; Condition; Development; Disease; Dopamine; Dopamine Receptor; Dose; Drug usage; Eating Disorders; Ensure; Environment; Ethical Issues; Female; Female Adolescents; Goals; Grant; Image; Incentives; Individual; Knowledge; Literature; Male Adolescents; Manuscripts; Mentored Research Scientist Development Award; Methods; Modeling; Motivation; Neurobiology; Pharmaceutical Preparations; Property; Public Health; Rattus; Research; Research Personnel; Research Training; Rewards; Self Administration; Sex Characteristics; Substance abuse problem; System; Techniques; Testing; Training; Translations; Writing; base; dopamine system; drug reward; food restriction; male; neurobiological mechanism; neurochemistry; pre-clinical; pre-clinical research; preclinical study; preference; psychostimulant; receptor; receptor density; response; sex; substance abuser

DESCRIPTION (provided by applicant): In this revised application for a K01 Mentored Research Scientist Development Award, Dr. Nicole Barbarich-Marsteller has proposed a comprehensive training and research plan in the translational neurobiology of substance abuse and eating disorders. There is significant comorbidity between these disorders and preclinical studies suggest that food restriction increases the reinforcing effects of psychostimulants; however, we are limited by 2 significant gaps in the literature that inhibit the translation of preclinical research on the effects of food restriction on drug reward into a better understanding of the relationship between clinical eating disorders and substance abuse. First, preclinical research has utilized adult rats, whereas the clinical onset of eating disorders and initial drug use typically occurs during adolescence. Second, preclinical research has focused on males, whereas the overwhelming majority of individuals with eating disorders and a significant proportion of substance abusers are females. The fact that there are sex-dependent changes in the dopamine receptor system during adolescence suggests there may be sex differences in the development of vulnerability to addictive behaviors during adolescence. Thus, the research aims of this grant are to use a multi-dimensional approach (conditioned place preference, self-administration, receptor density, microPET imaging) to identify how food restriction alters the behavioral and neurochemical response to psychostimulants during adolescence and to determine whether these effects are sex-dependent. The training goals for Dr. Barbarich-Marsteller are to: 1) acquire a more comprehensive knowledge of substance abuse and reward mechanisms; 2) gain expertise in sex-dependent, developmental aspects of the dopamine system and how they relate to addictive behaviors; 3) expand expertise in preclinical techniques for studying the dopamine system; 4) increase knowledge of the clinical relationship between substance abuse and eating disorders; and 5) increase proficiency in manuscript and grant writing and ethical issues in research. Overall, this award will ensure Dr. Barbarich-Marsteller's successful transition to an independent investigator. PUBLIC HEALTH RELEVANCE: The onset of substance abuse and eating disorders are increased during adolescence, yet the sex-dependent and neurobiological mechanisms that increase vulnerability during this period are not well understood. These studies will fill critical gaps in our understanding of adolescent reward mechanisms.

描述（由申请人提供）：在此修订的K01指导研究科学家发展奖的申请中，Nicole Barbarich-Marsteller博士提出了针对药物滥用和饮食失调的转化神经生物学的全面培训和研究计划。这些疾病和临床前研究之间存在着显着的合并症，这表明食物限制会增加心理刺激物的增强作用。但是，在文献中，我们受到了2个重大差距的限制，这些差距抑制了临床前研究对食物限制对药物奖励的影响的翻译，以更好地理解临床饮食失调与滥用药物之间的关系。首先，临床前研究利用了成年大鼠，而饮食失调的临床发作和初始吸毒通常发生在青春期。其次，临床前研究集中在男性上，而绝大多数饮食失调和大部分滥用药物的人都是女性。青春期多巴胺受体系统发生性别依赖性变化的事实表明，青春期脆弱性的发展可能存在性别差异。因此，该赠款的研究目的是使用多维方法（条件的位置偏好，自我管理，受体密度，微型tem成像）来确定食物限制如何改变对青春期心理刺激物的行为和神经化学反应，并确定这些效果是否与性别相关。 Barbarich-Marsteller博士的培训目标是：1）对药物滥用和奖励机制的更全面知识； 2）在多巴胺系统的性别依赖性，发展方面获得专业知识，以及它们如何与成瘾行为相关； 3）扩大研究多巴胺系统的临床前技术专业知识； 4）增加对药物滥用和饮食失调之间临床关系的了解； 5）提高手稿和赠款写作和研究道德问题的能力。总体而言，该奖项将确保Barbarich-Marsteller博士的成功过渡到独立调查员。 公共卫生相关性：青春期药物滥用和饮食失调的发作却增加了，但是在此期间增加脆弱性的性依赖性和神经生物学机制尚不清楚。这些研究将填补我们对青少年奖励机制的理解。