Functional studies of antidepressant exposure during adolescence on the brain

青春期抗抑郁药物暴露对大脑的功能研究

基本信息

批准号：
9222768
负责人：
Sergio Diaz Iniguez
金额：
$ 15.1万
依托单位：
UNIVERSITY OF TEXAS EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9222768
关键词：
20 year old Address Adolescence Adolescent Adult Aftercare Age Antidepressive Agents Anxiety Disorders Behavior Behavioral Behavioral Model Biochemical Biological Markers Biological Models Brain Brain region C57BL/6 Mouse CREB1 gene Child Childhood Chronic Cocaine Comorbidity Data Depressed mood Development Diagnosis Disease Disease Management Drug abuse Epidemiology Exposure to Female Fluoxetine Goals Hippocampal Formation Hippocampus (Brain)Intervention Investigation Life Link Long-Term Effects MAPK3 gene Major Depressive Disorder Mediating Mediation Memory Memory impairment Molecular Moods Morbidity - disease rate Mus Outcome Performance Pharmaceutical Preparations Pharmacology Phosphorylation Population Prevalence Principal Investigator Protein Kinase Proteins Regulation Reporting Rewards Ribosomal Protein S6 Kinase Ribosomes Risk Second Messenger Systems Selective Serotonin Reuptake Inhibitor Serotonin Signal Pathway Signal Transduction Signaling Molecule Site Stimulus Stress Substance abuse problem System Testing Women&apos s Group Work addiction antidepressant effect behavior influence behavioral response child depression conditioning drug of abuse drug reward drug seeking behavior emotional behavior experience experimental study extracellular insight male men&apos s group morris water maze mortality motivated behavior nerve supply neural circuit neuroadaptation neurobiological mechanism neurochemistry novel object recognition postnatal pre-clinical preference public health relevance response transcription factor treatment choice

项目摘要

DESCRIPTION (provided by applicant): Pediatric 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 a common condition. It is estimated that children and adolescents who suffer from MDD often develop conduct and anxiety disorders, and that up to 25% develop substance abuse disorder. Consequently, this has resulted in a disproportionate increase in the prevalence of antidepressants prescribed to populations below 20 years of age. Despite the heightened rates in antidepressant use, little is known about the potential long-term behavioral and neural adaptations resulting from antidepressant treatment during early development. To address this problem, the experiments described in this proposal will examine the long-term behavioral consequences of early life (postnatal day [PD] 35-49) exposure to fluoxetine, a selective serotonin reuptake inhibitor, using C57BL/6 male and female mice. This will be accomplished within the framework of the following specific aims: [1] assess long-term consequences of chronic adolescent antidepressant treatment on the sensitivity to reward (drug), mood related behaviors (stress), and memory in adulthood (PD80+), and [2] evaluate the integrity of mood-related biological markers [extracellular signal regulated protein kinase-1/2 (ERK)], within the hippocampal formation, following chronic adolescent antidepressant exposure. It is expected that antidepressant exposure during adolescence will induce long-lived alterations associated with responses to stress, drug-rewarded behaviors, and memory. Furthermore, it is expected that site-specific neurochemical adaptations (ERK fluctuations within the hippocampus) to be a factor mediating these behavioral alterations as a function of juvenile antidepressant exposure. Collectively, the results of this preclinical work will provide first-line evidence on the potential risks of antidepressant exposure during adolescence.

描述（适用提供）：直到几年前，小儿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），而且是一个普遍的疾病。据估计，患有MDD的儿童和青少年经常患上行为和焦虑症，高达25％的患者患药物滥用障碍。因此，这导致对20岁以下人群的抗抑郁药的患病率不成比例。尽管抗抑郁药的使用率提高，但对早期发育过程中抗抑郁治疗引起的潜在的长期行为和神经适应性知之甚少。为了解决这个问题，本提案中描述的实验将检查早期生命的长期行为后果（产后日[PD] 35-49）使用C57BL/6雄性和雌性小鼠氟西汀（一种选择性5-羟色胺再摄取抑制剂）暴露。这将在以下具体目的的框架内实现：[1]评估慢性青少年抗抑郁药对奖励的敏感性（药物），情绪相关行为（压力）和成年中的记忆（PD80+）（PD80+）（PD80+）的长期后果，并[2]评估了在情绪中估计的生物学标记（ERACELLACE SIGNAL INDICER SIGNAL）[2]慢性青少年暴露后，海马形成。预计青少年期间的抗抑郁药暴露会引起与压力，药物回报行为和记忆的反应有关的长寿变化。此外，预计位点特异性的神经化学适应（海马内的ERK波动）是介导这些行为改变的因素，这是青少年抗抑郁药暴露的函数。总的来说，这项临床前工作的结果将提供一线关于青少年期间抗抑郁药暴露的潜在风险的证据。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adolescent fluoxetine history impairs spatial memory in adult male, but not female, C57BL/6 mice

DOI：
10.1016/j.jad.2019.02.051
发表时间：
2019-04-15
期刊：
JOURNAL OF AFFECTIVE DISORDERS
影响因子：
6.6
作者：
Flores-Ramirez, Francisco J.;Parise, Lyonna F.;Iniguez, Sergio D.
通讯作者：
Iniguez, Sergio D.

Adolescent Fluoxetine Exposure Induces Persistent Gene Expression Changes in the Hippocampus of Adult Male C57BL/6 Mice.

DOI：
10.1007/s12035-020-02221-9
发表时间：
2021-04
期刊：
Molecular neurobiology
影响因子：
5.1
作者：
Iñiguez SD;Flores-Ramirez FJ;Themann A;Lira O
通讯作者：
Lira O

Dorsal Hippocampus ERK2 Signaling Mediates Anxiolytic-Related Behavior in Male Rats

DOI：
10.1177/2470547019897030
发表时间：
2019-01
期刊：
Chronic Stress
影响因子：
0
作者：
Jorge A Sierra-Fonseca;Lyonna F. Parise;F. Flores-Ramirez;E. Robles;Israel Garcia-Carachure;S. Iñiguez
通讯作者：
Jorge A Sierra-Fonseca;Lyonna F. Parise;F. Flores-Ramirez;E. Robles;Israel Garcia-Carachure;S. Iñiguez

Autophagy Induction and Accumulation of Phosphorylated Tau in the Hippocampus and Prefrontal Cortex of Adult C57BL/6 Mice Subjected to Adolescent Fluoxetine Treatment.

DOI：
10.3233/jad-210475
发表时间：
2021
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
0
作者：
Sierra-Fonseca JA;Rodriguez M;Themann A;Lira O;Flores-Ramirez FJ;Vargas-Medrano J;Gadad BS;Iñiguez SD
通讯作者：
Iñiguez SD

Ketamine beyond anesthesia: Antidepressant effects and abuse potential.