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）：直到几年前，童年抑郁症几乎是不可想象的。现在我们不仅知道儿童和青少年存在重度抑郁症（MDD），而且它也是一种常见病症。早年 MDD 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出现行为障碍和焦虑障碍，其中 20-25% 会出现药物滥用障碍。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。尽管抗抑郁药物的使用率很高，但人们对成年前抗抑郁治疗所导致的长期行为和神经适应却知之甚少。为了满足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（出生后第35天）抗抑郁药治疗的行为反应，并将进一步评估青春期抗抑郁药的长期行为后果成年期治疗（PD90+）。这将在以下具体目标的框架内完成：[1]确定幼年大鼠抗抑郁治疗的疗效，[2]评估长期青少年抗抑郁治疗对奖赏（自然，药物）敏感性的长期影响以及成年期与情绪相关（焦虑、压力）的行为，以及 [3] 评估中脑边缘系统内与奖赏相关的生物标志物 [细胞外信号调节蛋白激酶 (ERK)] 的完整性。抗抑郁药暴露。我们预计，青春期期间接触抗抑郁药物会引起与压力、焦虑、自然和药物奖励行为的反应相关的长期改变。此外，我们预计位点特异性神经化学改变（腹侧被盖区内的 ERK 波动）是调节这些情绪和奖励相关改变的一个因素，作为早期抗抑郁药物暴露的函数。