Long-Term Consequences of Antidepressant Exposure During Adolescence in Male Rats

雄性大鼠青春期暴露于抗抑郁药物的长期后果

• 批准号: 7752674
• 负责人: Sergio Diaz Iniguez
• 金额: $ 3.09万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-09 至 2012-08-08
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7752674
• 关键词: 20 year old; Acute; Address; Adolescence; Adolescent; Adult; Antidepressive Agents; Antisocial Personality Disorder; Anxiety; Anxiety Disorders; Behavior; Behavioral; Biochemical; Biological Markers; Bipolar Disorder; Child; Childhood; Chronic; Cocaine; Depressive disorder; Diagnosis; Disease; Dose; Fluoxetine; Knowledge; Life; Major Depressive Disorder; Male Adolescents; Mediating; Moods; Morbidity - disease rate; Pathway interactions; Pharmaceutical Preparations; Population; Prevalence; Protein Biochemistry; Protein Kinase; Rattus; Reporting; Rewards; Role; Signal Transduction; Site; Stress; Substance abuse problem; Sucrose; Suicide; Swimming; Techniques; Testing; Ventral Tegmental Area; Viral Vector; Youth; depression; drug reward; extracellular; immunocytochemistry; male; mesolimbic system; mortality; neuroadaptation; neurochemistry; postnatal; research study; response

DESCRIPTION (provided by applicant): Childhood depression was almost unthinkable until several years ago. Now we not only know that major depressive disorder (MDD) exists in children and adolescents, but that it is also a common condition. Early-life MDD has been correlated with antisocial personality, bipolar disorder, and suicide. It is estimated that youngsters who suffer from depression often develop conduct and anxiety disorders, and that 20-25% develop substance abuse disorder. Consequently, this has resulted in a disproportionate increase in the prevalence of, antidepressants prescribed to youths below 20 years of age. Despite the heightened rates in antidepressant use, little is known about the long-term behavioral and neural adaptations resulting from antidepressant treatment during periods before adulthood. To address this need in our basic knowledge, the experiments described in this proposal will examine the behavioral responses to antidepressant treatment in "adolescent" rats (postnatal day [PD] 35), and will further assess the long-term behavioral consequences of adolescent antidepressant treatment in adulthood (PD90+). This will be accomplished within the framework of the following specific aims: [1] determine the efficacy of antidepressant treatment in juvenile rats, [2] assess long-term consequences of chronic adolescent antidepressant treatment on the sensitivity to reward- (natural, drug) and mood-related (anxiety, stress) behaviors in adulthood, and [3] evaluate the integrity of reward-related biological markers [extracellular signal regulated protein kinase (ERK)], within the mesolimbic system, following chronic adolescent antidepressant exposure. We expect that antidepressant exposure during adolescence will induce long-lived alterations associated with responses to stress, anxiety, natural- and drug-rewarded behaviors. Furthermore, we expect site-specific neurochemical alterations (ERK fluctuations within the ventral tegmental area) to be a factor mediating these mood- and reward-related alterations as a function of early-life antidepressant exposure.

描述（由申请人提供）：儿童抑郁症几乎是不可想象的，直到几年前。现在我们不仅知道重度抑郁症（MDD）存在于儿童和青少年中，而且它也是一种常见的疾病。早期抑郁症与反社会人格、双相情感障碍和自杀有关。据估计，患有抑郁症的青少年往往会发展为行为和焦虑障碍，20-25%的青少年会发展为物质滥用障碍。因此，这导致20岁以下青少年服用抗抑郁药的比例不成比例地增加。尽管抗抑郁药的使用率提高，但人们对成年前抗抑郁药治疗引起的长期行为和神经适应知之甚少。为了解决我们基础知识中的这一需求，本提案中描述的实验将检查“青春期”大鼠（出生后[PD] 35天）对抗抑郁药治疗的行为反应，并将进一步评估成年期（PD 90+）青少年抗抑郁药治疗的长期行为后果。这将在以下具体目标的框架内实现：[1]确定抗抑郁药治疗在幼年大鼠中的疗效，[2]评估慢性青少年抗抑郁药治疗对奖励敏感性的长期影响-（自然的、药物的）和情绪相关的（焦虑，压力）行为，和[3]评价慢性青少年抗抑郁药暴露后中脑边缘系统内奖赏相关生物标志物[细胞外信号调节蛋白激酶（ERK）]的完整性。我们预计，在青春期抗抑郁药的暴露将导致长期的变化与压力，焦虑，自然和药物奖励行为的反应。此外，我们预计特定位点的神经化学变化（腹侧被盖区内的ERK波动）是一个因素，介导这些情绪和奖励相关的变化作为一个功能的早期生活抗抑郁药暴露。