Cocaine Alterations of Maternal Dopamine Transients

可卡因对母亲多巴胺瞬变的改变

• 批准号: 8583015
• 负责人: Donita L Robinson
• 金额: $ 7.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8583015
• 关键词: Age; Animal Experimentation; Auditory; Behavior; Behavior Control; Behavioral; Biochemical; Birth; Caring; Characteristics; Chronic; Cocaine; Complex; Crying; Cues; Data; Detection; Dopamine; Etiology; Event; Excision; Exhibits; Female; Food; Foundations; Frequencies; Grooming; Grouping; Hormonal; Human; Individual; Infant; Intervention; Lead; Locomotion; Maternal Behavior; Measures; Monitor; Mothers; Neurobiology; Neuropeptides; Nucleus Accumbens; Odors; Pathway interactions; Pattern; Pharmaceutical Preparations; Postpartum Period; Pregnancy; Rattus; Relative (related person); Retrieval; Rewards; Rodent; Rodent Model; Role; Sampling; Scanning; Signal Transduction; Solid; Stimulus; Substance abuse problem; Testing; Time; Touch sensation; Urine; Ventral Striatum; Visual; approach behavior; cocaine exposure; cocaine use; cocaine-exposed infant; comparative efficacy; comparison group; maternal cocaine use; maternal drug abuse; motivated behavior; neglect; neurochemistry; neuromechanism; non-drug; offspring; olfactory stimulus; public health relevance; pup; reinforcer; relating to nervous system; research study; response; sex; social; transmission process; vocalization

DESCRIPTION (provided by applicant): Disruption of maternal behavior by substance abuse resulting in higher levels of maternal neglect towards infants is well documented in human and animal research, while the associated neural mechanisms remain unclear. Several rodent studies indicate that cocaine-exposed maternal females may be less motivated to spend time with pups compared to non-cocaine exposed mothers. One possibility is that pup stimuli, which are known to promote maternal responding in normal mothers, are perceived as less motivating in cocaine-exposed mothers. Motivated behaviors are modulated by dopamine activity in the mesoaccumbens pathway. Fast dopamine release events in the ventral striatum, i.e. dopamine transients, are neural signals of reward prediction occurring at the detection of salient stimuli and often precede approach to a reinforcer. We hypothesize that dopamine transients in rat mothers are triggered by pup stimuli and facilitate normal pup-directed maternal behaviors, while cocaine-treated mothers have blunted DA release to stimuli from their pups that correlates with less maternal response and is driven by a combination of maternal dopamine alterations to cocaine and altered stimuli produced by the cocaine-exposed pups. We propose to use fast scan cyclic voltammetry to measure dopamine release in an established rodent model of maternal behavior. Thus, we will determine whether maternal cocaine exposure during pregnancy, which reduces pup-directed behaviors, also diminishes maternal dopamine release to pup cues. We will use a two-step approach: we will profile dopamine transients in rodent mothers first as they respond to their litters, and second in response to selected pup cues separately from the whole litter. Together, results from these experiments will (1) determine relationships between specific pup-associated stimuli, normal maternal behavior and dopamine transients, and (2) verify how gestational cocaine use alters these relationships in the mother-infant dyad. The data from these studies will provide a solid foundation for future research concerning the causality and biochemical underpinnings of phasic dopamine signals in maternal behavior and their dysregulation by chronic cocaine and will inform our understanding of human maternal neglect in drug-abusing mothers.

描述（由申请人提供）：药物滥用对母亲行为的破坏导致母亲对婴儿的更高程度的忽视，在人类和动物研究中有很好的记录，但相关的神经机制尚不清楚。几项啮齿动物研究表明，与未接触可卡因的母鼠相比，接触可卡因的母鼠可能更不愿意花时间与幼鼠在一起。一种可能性是，幼犬的刺激在正常母亲中被认为能促进母亲的反应，但在暴露于可卡因的母亲中却被认为不那么有动力。动机行为是由中伏隔核通路中的多巴胺活动调节的。腹侧纹状体中的快速多巴胺释放事件，即多巴胺瞬态，是在检测到显著刺激时发生的奖励预测的神经信号，通常发生在强化物接近之前。我们假设，母鼠体内的多巴胺瞬变是由幼鼠刺激触发的，并促进了正常的幼鼠指导的母鼠行为，而可卡因治疗的母鼠对幼鼠刺激的DA释放减弱，这与母鼠的反应减少有关，这是由母鼠多巴胺对可卡因的改变和暴露于可卡因的幼鼠产生的改变刺激共同驱动的。我们建议使用快速扫描循环伏安法测量多巴胺释放在一个已建立的啮齿动物模型的母性行为。因此，我们将确定母体在怀孕期间暴露于可卡因是否会减少幼犬的定向行为，也会减少母体对幼犬的多巴胺释放。我们将采用两步的方法：我们将首先分析啮齿动物母亲对其产仔的反应时的多巴胺瞬变，其次是对与整个产仔分开的选定幼仔线索的反应。总之，这些实验的结果将(1)确定特定幼崽相关刺激，正常母亲行为和多巴胺瞬变之间的关系，以及(2)验证妊娠期可卡因使用如何改变母婴双体中的这些关系。这些研究的数据将为进一步研究母体行为中阶段性多巴胺信号的因果关系和生化基础以及它们在慢性可卡因作用下的失调提供坚实的基础，并将为我们理解吸毒母亲的人类母亲忽视提供信息。