Brain Imaging of Cocaine and Maternal Reward

可卡因的脑成像与母亲奖励

• 批准号: 7665379
• 负责人: MARCELO FEBO
• 金额: $ 31.85万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7665379
• 关键词: Affect; Area; Autoradiography; Behavior; Binding; Biological Neural Networks; Brain; Brain imaging; Child; Chronic; Clinical; Cocaine; Cocaine Dependence; Complement; Cues; Data; Development; Discipline of Nursing; Distal; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Functional Magnetic Resonance Imaging; Home environment; Housing; Image; In Vitro; Infant; Intervention; Lactation; Maternal Behavior; Measures; Medial; Methods; Microdialysis; Mothers; Neurons; Newborn Infant; Nipples; Nucleus Accumbens; Nurses; Pharmaceutical Preparations; Phase; Plastics; Postpartum Period; Prefrontal Cortex; Rattus; Research; Retrieval; Rewards; Role; Signal Transduction; Simulate; Site; Slice; Testing; Time; blood oxygenation level dependent response; brain tissue; dopamine transporter; experience; extracellular; in vivo; neuromechanism; neurotransmission; psychosocial; pup; receptor; receptor density; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): Lactation provides a rewarding experience beneficial to mother-infant bonding. Cocaine addiction can sever this critical mother-infant experience, possibly affecting child psychosocial development. The main hypothesis of the proposed research is that adaptations in mesocortical dopamine function, long after chronic cocaine administration, affect maternal responsiveness to newborns. Functional MRI, in vivo microdialysis and autoradiographic methods will be employed to identify neural networks activated by suckling, a natural reward in lactating rats. Two specific aims are proposed. 1) It is hypothesized that the medial prefrontal cortex (mPFC) of cocaine sensitized dams is less responsive to suckling but will be activated by distal presentation of pups (supporting a greater appetitive drive). To test this, the neural response to distal presentation of pups or suckling stimulation is imaged in drug naive and cocaine sensitized dams. During imaging sessions, pups are housed in a special cradle that controls access to nipples or a clear plastic vivarium that simulates the maternal home cage. These data will be complemented by experiments testing for appetitive and consummately components of maternal behaviors in control and cocaine sensitized mothers. Alterations in response to suckling pups or pup cues will be accompanied by increased dopamine (DA) transporter (DAT) function with concomitant changes in extracellular DA and its receptors in the mPFC. 2) It is hypothesized that the appetitive and consummatory components of maternal responding are modulated by dopamine signaling mechanisms in the mPFC. To test this, cocaine sensitized and control mothers are given an intra-mPFC D1-, D2-like DA receptor or DAT blocker and appetitive and consummatory maternal responses analyzed. In specific aim 2, DAT binding and D1 and D2 receptor density will be assessed in brain tissue slices and mPFC DA levels measured in response to suckling pups. The studies in Specific Aim 2 will also examine DA function in the nucleus accumbens, a brain area associated, with reward seeking behavior. By understanding the neural mechanisms underlying maternal behaviors and the role of mPFC DA in the expression of these behaviors, it will be possible to target brain substrates for clinical intervention in mothers recovering from cocaine addiction.

描述（由申请人提供）：哺乳期提供了有益的经验，有利于母婴债券。可卡因成瘾可以切断这种关键的母婴体验，可能影响儿童的心理社会发展。这项研究的主要假设是，长期服用可卡因后，中皮层多巴胺功能的适应性会影响母体对新生儿的反应。功能性磁共振成像，在体内微透析和放射自显影方法将被用来确定哺乳，哺乳大鼠的自然奖励激活的神经网络。提出了两个具体目标。1)假设可卡因致敏母鼠的内侧前额叶皮层（mPFC）对哺乳反应较低，但将被幼仔的远端呈递激活（支持更大的食欲驱动）。为了测试这一点，在未用药和可卡因致敏的母鼠中对幼仔远端呈递或吮吸刺激的神经反应进行成像。在成像过程中，幼崽被安置在一个特殊的摇篮中，控制乳头或一个透明的塑料动物园，模拟母亲的家笼。这些数据将通过测试对照组和可卡因致敏母亲的母亲行为的食欲和消耗成分的实验来补充。对哺乳幼仔或幼仔线索的反应变化将伴随多巴胺（DA）转运蛋白（DAT）功能增加，伴随细胞外DA及其在mPFC中的受体的变化。2)据推测，食欲和完善的组成部分，母亲的反应调制的多巴胺信号机制中的mPFC。为了测试这一点，可卡因致敏和对照组的母亲给予内mPFC D1，D2样DA受体或DAT阻滞剂和食欲和完善的母亲的反应进行了分析。在具体目标2中，将在脑组织切片中评估DAT结合以及D1和D2受体密度，并测量哺乳幼仔的mPFC DA水平。具体目标2中的研究还将检查多巴胺在脑桥核中的功能，脑桥核是一个与奖励寻求行为相关的大脑区域。通过了解母体行为的神经机制和mPFC DA在这些行为表达中的作用，将有可能针对可卡因成瘾母亲的临床干预脑基质。