Brain Imaging of Cocaine and Maternal Reward
可卡因的脑成像与母亲奖励
基本信息
- 批准号:8101966
- 负责人:
- 金额:$ 30.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-08-01 至 2013-07-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAreaAutoradiographyBehaviorBindingBiological Neural NetworksBrainBrain imagingChildChronicClinicalCocaineCocaine DependenceComplementCuesDataDevelopmentDiscipline of NursingDistalDopamineDopamine D1 ReceptorDopamine D2 ReceptorDopamine ReceptorFunctional Magnetic Resonance ImagingHome environmentHousingImageIn VitroInfantInterventionLactationMaternal BehaviorMeasuresMedialMethodsMicrodialysisMothersNeuronsNewborn InfantNipplesNucleus AccumbensPharmaceutical PreparationsPhasePlasticsPostpartum PeriodPrefrontal CortexRattusResearchRetrievalRewardsRoleSignal TransductionSimulateSiteSliceTestingTimeblood oxygenation level dependent responsebrain tissuedopamine transporterexperienceextracellularin vivoneuromechanismneurotransmissionpsychosocialpupreceptorreceptor densityrelating to nervous systemresearch studyresponse
项目摘要
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体验,有利于母婴关系。可卡因成瘾可能会破坏这种重要的母婴体验,可能会影响儿童的社会心理发展。该研究的主要假设是,在长期服用可卡因后很长时间内,中皮质多巴胺功能的适应会影响母亲对新生儿的反应。将采用功能性 MRI、体内微透析和放射自显影方法来识别由哺乳激活的神经网络,这是哺乳期大鼠的自然奖励。提出了两个具体目标。 1) 据推测,可卡因致敏的母鼠的内侧前额叶皮层 (mPFC) 对哺乳的反应较弱,但会被幼崽的远端呈现所激活(支持更大的食欲驱动力)。为了测试这一点,在未接受药物和可卡因致敏的母鼠中对幼鼠远端呈现或哺乳刺激的神经反应进行了成像。在成像过程中,幼崽被安置在一个特殊的摇篮中,该摇篮可以控制乳头的接触,或者是一个模拟母体笼子的透明塑料饲养箱。这些数据将通过测试对照母亲和可卡因过敏母亲的食欲和完美母亲行为组成部分的实验来补充。对哺乳幼崽或幼崽提示的反应的改变将伴随着多巴胺 (DA) 转运蛋白 (DAT) 功能的增加,以及胞外 DA 及其在 mPFC 中的受体的变化。 2) 假设母体反应的食欲和完成成分是由 mPFC 中的多巴胺信号机制调节的。为了测试这一点,可卡因致敏和对照母亲被给予 mPFC 内 D1、D2 样 DA 受体或 DAT 阻滞剂,并分析食欲和完成的母亲反应。在具体目标 2 中,将评估脑组织切片中的 DAT 结合以及 D1 和 D2 受体密度,并测量对哺乳幼崽的反应,测量 mPFC DA 水平。具体目标 2 中的研究还将检查伏隔核(与奖励寻求行为相关的大脑区域)中的 DA 功能。通过了解母亲行为背后的神经机制以及 mPFC DA 在这些行为表达中的作用,将有可能针对大脑基质对从可卡因成瘾中恢复的母亲进行临床干预。
项目成果
期刊论文数量(24)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.
- DOI:10.1016/j.drugalcdep.2013.09.032
- 发表时间:2014-01-01
- 期刊:
- 影响因子:4.2
- 作者:Caffrey MK;Febo M
- 通讯作者:Febo M
Brain Reward Pathway Dysfunction in Maternal Depression and Addiction: A Present and Future Transgenerational Risk.
- DOI:10.17756/jrds.2015-017
- 发表时间:2015
- 期刊:
- 影响因子:0
- 作者:Nephew BC;Murgatroyd C;Pittet F;Febo M
- 通讯作者:Febo M
Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift: Dopamine for Dinner?
- DOI:10.1007/s12035-015-9110-9
- 发表时间:2015-12
- 期刊:
- 影响因子:5.1
- 作者:Blum K;Febo M;Thanos PK;Baron D;Fratantonio J;Gold M
- 通讯作者:Gold M
Behavioral effects of acclimatization to restraint protocol used for awake animal imaging.
- DOI:10.1016/j.jneumeth.2013.03.023
- 发表时间:2013-07-15
- 期刊:
- 影响因子:3
- 作者:Reed, Michael D.;Pira, Ashley S.;Febo, Marcelo
- 通讯作者:Febo, Marcelo
Addiction Treatment in America: After Money or Aftercare?
- DOI:10.17756/jrds.2015-015
- 发表时间:2015-10
- 期刊:
- 影响因子:0
- 作者:David K. Miller;Merlene Miller;K. Blum;R. Badgaiyan;M. Febo
- 通讯作者:David K. Miller;Merlene Miller;K. Blum;R. Badgaiyan;M. Febo
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{{ truncateString('MARCELO FEBO', 18)}}的其他基金
Imaging In Vivo Neural Mechanisms of Synthetic Cathinones (Bath Salts)
合成卡西酮(浴盐)的体内神经机制成像
- 批准号:
9015421 - 财政年份:2015
- 资助金额:
$ 30.59万 - 项目类别:
Imaging In Vivo Neural Mechanisms of Synthetic Cathinones (Bath Salts)
合成卡西酮(浴盐)的体内神经机制成像
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8892408 - 财政年份:2015
- 资助金额:
$ 30.59万 - 项目类别:
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