COCAINE & MATERNAL AGGRESSION--OXYTOCINERGIC MECHANISMS

可卡因

• 批准号: 6607455
• 负责人: Josephine M. Johns
• 金额: $ 28.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6607455
• 关键词: aggression; amitriptyline; amygdala; autoradiography; behavioral /social science research tag; cocaine; desipramine; embryo /fetus toxicology; fluoxetine; hormone receptor; hormone regulation /control mechanism; in situ hybridization; laboratory rat; lactation; maternal behavior; oxytocin; paraventricular nucleus; postpartum; pregnancy; preoptic areas; psychopharmacology; radioimmunoassay; receptor binding; tegmentum

DESCRIPTION (applicant's abstract): Cocaine abuse by human mothers is correlated with a high incidence of child neglect and abuse. Gestational cocaine (COC) treatment has been shown to increase aggression towards an intruder (maternal aggression) and reduce the levels of oxytocin (OXY) in the amygdala of rats on postpartum days (PPD) 6-10. Blocking OXY receptors in the central amygdala results in an increase in aggression parallel to that seen following COC treatment. COC likely decreases OXY in the amygdala and increases maternal aggression through its reuptake inhibition of dopamine (DA), serotonin (5-HT) and norepinephrine (NE). These studies are designed to elucidate the specific mechanisms through which COC may work to alter OXY and maternal aggression in rats. Specific Aim 1 will determine if gestational treatment with a combination treatment of selective DA and 5-HT uptake inhibitor will increase maternal aggression as does COC. To test this hypothesis, groups of rat dams will be treated gestationally (days 1-20) with COC, control vehicle buffer (VCB), selective DA, 5-HT, or NE reuptake inhibitors or combinations of selective inhibitors. Dams will be tested for maternal aggression on PPD 6. Specific Aim 2 will determine if gestational treatment with a combination of a selective DA and 5-HT uptake inhibitor will alter OXY dynamics as does COC. To test this hypothesis, groups of rat dams will be treated gestationally (days 1-20) with vehicle buffer (VCB), COC, selective DA, 5-HT, or NE reuptake inhibitors or combinations of the selective inhibitors and sacrificed on PPD 6. OXY levels and receptor binding will be measured by radioimmunoassay, in situ hybridization and autoradiography in the amygdala, medial preoptic area and paraventricular nucleus of the hypothalamus, all of which have been implicated in OXY regulation of maternal aggression. Specific Aim 3 will determine if gestational COC treatment reduces OXY synthesis in the medial preoptic area and paraventricular nucleus and oxytocin receptor (OTR) synthesis in the amygdala, medial preoptic area and paraventricular nucleus. To test this hypothesis, rat dams will be treated gestationally with VCB or COC, and these brain regions removed for in situ hybridization and autoradiography for assessment of OXY and OTR messenger ribonucleic acid on PPD 6. Specific Aim 4 will determine if prenatal exposure to COC and being raised by a COC treated mother as compared to being raised by mothers treated with control vehicle increases maternal aggression displayed by female offspring and decreases OXY in the amygdala of the offspring as adults. To test this hypothesis, female offspring of dams gestationally treated with COC or control vehicle buffer (2 groups, buffer with no pair feeding and buffer with pair feeding), will be raised by their natural dams or foster dams that are vehicle-treated (pair-fed and non-pair-fed) or COC and then bred and tested for maternal aggression in the presence of their own litters on PPD 6. OXY levels in the amygdala will be assessed following the behavioral testing.

描述（申请人摘要）：人类母亲滥用可卡因是 与儿童忽视和虐待的高发率有关。妊娠 可卡因（COC）治疗已被证明会增加对 入侵者（母亲的侵略）和减少催产素（OXY）的水平， 产后第6-10天大鼠杏仁核（PPD）。阻断OXY受体， 中央杏仁核导致攻击性的增加， COC治疗后。COC可能会减少杏仁核中的OXY， 母体攻击通过其再摄取抑制多巴胺（DA），血清素 （5-HT）和去甲肾上腺素（NE）。这些研究旨在阐明 COC可能通过特定机制改变OXY和母体 老鼠的攻击性 具体目标1将确定妊娠期治疗是否与联合用药 选择性DA和5-HT摄取抑制剂的治疗将增加母体 COC也有攻击性。为了验证这一假设，将对大鼠母鼠进行分组， 妊娠期（第1-20天）用COC、对照载体缓冲液（VCB）， 选择性DA、5-HT或NE再摄取抑制剂或选择性 抑制剂的将在PPD 6时检测母体攻击性。 具体目标2将确定妊娠期治疗是否与 选择性DA和5-HT摄取抑制剂将像COC一样改变OXY动力学。到 为了检验这一假设，将对大鼠母鼠组进行妊娠处理（天 1-20）与溶媒缓冲液（VCB）、COC、选择性DA、5-HT或NE再摄取 抑制剂或选择性抑制剂的组合，并在PPD 6时处死。 将通过放射免疫测定法原位测量OXY水平和受体结合 杏仁核、内侧视前区和 下丘脑室旁核，所有这些都与 母亲攻击性的氧合调节。 具体目标3将确定妊娠期COC治疗是否会减少OXY 内侧视前区和室旁核的合成与催产素 杏仁核、内侧视前区和视后区的OTR受体合成 室旁核为了检验这一假设，将对大鼠母鼠进行处理 妊娠时使用VCB或COC，并将这些大脑区域移除以进行原位 杂交和放射自显影用于评估OXY和OTR信使 PPD 6上的核糖核酸。 具体目标4将确定产前接触COC和由一个 COC治疗的母亲与对照组母亲相比 载体增加雌性后代表现出的母性攻击性， 减少了成年后的后代杏仁核中的氧合酶。为了验证这一 假设，接受COC或对照妊娠处理的母鼠的雌性后代 车辆缓冲器（2组，无对送料缓冲器和有对送料缓冲器 饲养），将提高他们的自然大坝或培育大坝， 媒介物处理（成对饲喂和非成对饲喂）或COC，然后进行饲养和检测 在PPD 6时，母亲在自己的窝仔面前表现出攻击性。氧合水平 在行为测试之后将对杏仁核进行评估。