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（申请人的摘要）：人母亲滥用可卡因是 与儿童忽视和虐待的高发生率有关。妊娠 可卡因（COC）的治疗已显示可增加侵略性 入侵者（母体攻击）并降低催产素（氧）的水平 在产后天（PPD）6-10的大鼠杏仁核。阻止氧气受体 中央杏仁核导致平行于侵略性的增加 COC处理后。 COC可能会减少杏仁核中的氧气，并增加 孕产妇通过其再摄取抑制多巴胺（DA），5-羟色胺的侵略性 （5-HT）和去甲肾上腺素（NE）。这些研究旨在阐明 COC可以通过的特定机制来改变氧气和母体 大鼠侵略。 具体目标1将确定妊娠治疗是否与组合 选择性DA和5-HT摄取抑制剂的治疗将增加母体 侵略性和COC一样。为了检验这一假设，大鼠大坝将是 用COC，控制车辆缓冲液（VCB）对妊娠（第1-20天）进行处理， 选择性DA，5-HT或NE再摄取抑制剂或选择性的组合 抑制剂。大坝将在PPD 6上测试母体侵略。 特定的目标2将确定妊娠治疗是否与 选择性DA和5-HT摄取抑制剂将像COC一样改变氧化动力学。到 检验该假设，将对大鼠大坝组进行妊娠治疗（天 1-20）使用车辆缓冲区（VCB），COC，选择性DA，5-HT或NE重新摄取 选择性抑制剂的抑制剂或组合，并在PPD 6上处死。 氧气水平和受体结合将通过放射免疫测量，原位测量 杏仁核，内侧前区域的杂交和放射自显影 下丘脑的副核核，所有这些都与 在孕产妇侵略的氧气调节中。 特定的目标3将确定妊娠COC治疗是否减少了氧气 内侧前区域的合成和旁牙核和催产素的合成 杏仁核，内侧前区域的受体（OTR）合成 副核核。为了检验该假设，将处理大鼠大坝 用VCB或COC妊娠，这些大脑区域被去除以原位 用于评估Oxy和OTR Messenger的杂交和放射自显影 PPD 6上的核糖酸。 具体目标4将确定产前暴露于COC并被A凸起 与受控治疗的母亲相比，COC治疗的母亲相比 车辆增加了女性后代表现出的母亲侵略性 成年后后代的杏仁核中减少氧气。测试这个 假设，用COC或对照治疗的大坝的女性后代 车辆缓冲液（2组，缓冲液，没有配对，带有配对的缓冲液 喂养），将由其天然大坝或寄养大坝饲养 媒介物处理（配对和非对配喂养）或COC，然后进行繁殖和测试 在ppd 6上存在自己的垃圾的情况下，母亲的侵略。氧气水平 在行为测试之后，将评估杏仁核。