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，儿童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大抑郁症（MDD），而且这也是一个普遍的疾病。早期MDD与反社会个性，躁郁症和自杀有关。据估计，患有抑郁症的年轻人经常患上行为和焦虑症，而20-25％的年轻人患有药物滥用障碍。因此，这导致对20岁以下青年的抗抑郁药的患病率的不成比例增加。尽管抗抑郁药的使用率提高，但对成年期间抗抑郁治疗引起的长期行为和神经适应性知之甚少。为了解决我们的基本知识，本提案中描述的实验将检查“青春期”大鼠（产后日[PD] 35）中对抗抑郁药治疗的行为反应，并将进一步评估成年中青少年抗抑郁治疗的长期行为后果（PD90+）。这将在以下特定目的的框架内实现：[1]确定抗抑郁药在少年大鼠中的疗效，[2]评估慢性青少年抗抑郁药对奖励（自然，药物）和情绪相关（焦虑，焦虑，压力）的长期后果，并评估了奖励的奖励，[3]评估了奖励的奖励，[3]评估了奖励的奖励。慢性青少年抗抑郁药暴露后，在中脑膜系统内激酶（ERK）]。我们预计，青春期抗抑郁药的暴露会引起与压力，焦虑，自然和药物训练行为的反应有关的长期变化。此外，我们预计位点特异性的神经化学改变（腹侧对段区域内的ERK波动）是介导这些与情绪和奖励相关的改变，这是早期抗抑郁药暴露的函数。