EARLY EXPERIENCE ALTERS ADULT BEHAVIOR AND THE HPA AXIS

早期经历改变成人行为和 HPA 轴

• 批准号: 6476994
• 负责人: PAUL M PLOTSKY
• 金额: $ 25.8万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6476994
• 关键词: amygdala; animal developmental psychology; antidepressants; arginine vasopressin; behavioral /social science research tag; benzodiazepine receptor; corticotropin releasing factor; early experience; environmental stressor; genetic transcription; hormone regulation /control mechanism; hypothalamic pituitary adrenal axis; laboratory rat; microdialysis; mother deprivation; neurochemistry; neuroendocrine system; neuropharmacology; psychological stressor; receptor expression; stress

DESCRIPTION (adapted from applicant's abstract): Both basic and epidemiological studies implicate psychosocial stressors and life events in the development of affective disorders. This stress diathesis model is partially based on the findings that a traumatic stressor often precedes the onset of affective episodes. Accumulating evidence strengthens the concept that the experience of early trauma serves as an important vulnerability factor in this sequelae. Dysfunction of one or more neuronal systems has been postulated in the etiology of major affective disorders, including the noradrenergic (NA) system, the serotonergic (5-HT) system, and the hypothalamic-pituitary-adrenal (HPA) axis. Clinical and animal studies have identified apparent dysregulation of the HPA axis in major depression and its experimental analogs. Dysregulation includes resistance to glucocorticoid negative feedback, elevated concentrations of corticotropin-releasing factor (CRF) in the CSF and/or in specific neuronal structures, and alterations in either peripheral and/or central glucocorticoid receptor density. In animals studies administration of exogenous CRF not only produces activation of the HPA axis, but is associated with many symptoms of depression. Given this burgeoning evidence for a major role for CRF in the pathogenesis of affective disorders coupled with the observed psychiatric impact of early trauma, the investigators hypothesize that early trauma such as that induced by maternal deprivation or abuse may modify hypothalamic and/or extrahypothalamic CRF neurons and may alter inputs to these CRF neurocircuits in such a way as to produce neurochemical, endocrine, and behavioral hyperresponsivity to stressors in adults. Their recent research utilizing neonatal maternal separation in rats has not only verified the existence of alterations in the function of central CRF systems of glucocorticoid receptor density associated with early traumatic experience, but has also uncovered evidence supporting the involvement of adrenergic, serotonergic and GABAergic/benzodiazapine (BZ) systems in either mediating and/or maintaining these maladaptive alterations. In the current application, the investigators propose to further characterize these changes, to elucidate the mechanisms underlying these changes and to evaluate the potential of pharmacological interventions to reverse these dysfunctions. Overall, this research will augment understanding of the role of perinatal life expereince in the development of individual differences in stress responsiveness as well as in identification of neural processes that define this vulnerability.

描述（改编自申请人摘要）：基本和

项目成果

Locus Coeruleus Noradrenergic Modulation of Diurnal Corticosterone, Stress Reactivity, and Cardiovascular Homeostasis in Male Rats.

• DOI: 10.1159/000520192
• 发表时间: 2022
• 期刊: Neuroendocrinology
• 影响因子: 4.1

Adverse early life experience and social stress during adulthood interact to increase serotonin transporter mRNA expression.

• DOI: 10.1016/j.brainres.2009.09.065
• 发表时间: 2009-12-11
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Gardner KL;Hale MW;Lightman SL;Plotsky PM;Lowry CA
• 通讯作者: Lowry CA

Adverse experience during early life and adulthood interact to elevate tph2 mRNA expression in serotonergic neurons within the dorsal raphe nucleus.

• DOI: 10.1016/j.neuroscience.2009.07.055
• 发表时间: 2009-11-10
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Gardner, K. L.;Hale, M. W.;Oldfield, S.;Lightman, S. L.;Plotsky, P. M.;Lowry, C. A.
• 通讯作者: Lowry, C. A.