Cocaine Alterations of Maternal Dopamine Transients

可卡因对母亲多巴胺瞬变的改变

• 批准号: 9066268
• 负责人: Donita L Robinson
• 金额: $ 0.67万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9066268
• 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; Health; 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; neurotransmission; non-drug; offspring; olfactory stimulus; pup; reinforcer; 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）：人类和动物研究中充分记录了药物滥用对母亲行为的干扰，导致母亲对婴儿的忽视程度更高，但相关的神经机制仍不清楚。几项啮齿动物研究表明，与未接触过可卡因的母亲相比，接触过可卡因的母亲可能不太愿意花时间陪伴幼崽。一种可能性是，众所周知，幼崽的刺激可以促进正常母亲的母亲反应，但在接触可卡因的母亲中却被认为没有那么积极性。动机行为由中伏隔通路中的多巴胺活性调节。腹侧纹状体中的快速多巴胺释放事件，即多巴胺瞬变，是在检测到显着刺激时发生的奖励预测的神经信号，并且通常先于接近强化物。我们假设，大鼠母亲体内的多巴胺瞬变是由幼崽刺激触发的，并促进正常的幼崽导向的母体行为，而接受可卡因治疗的母亲则减弱了幼崽对刺激的 DA 释放，这与母体反应较少相关，并且是由母体多巴胺对可卡因的改变和可卡因暴露产生的刺激改变共同驱动的。 小狗。我们建议使用快速扫描循环伏安法来测量已建立的啮齿动物母体行为模型中的多巴胺释放。因此，我们将确定母亲在怀孕期间接触可卡因，这会减少幼崽导向的行为，是否也会减少母体对幼崽线索的多巴胺释放。我们将采用两步方法：首先，我们将分析啮齿类动物母亲对其幼仔做出反应时的多巴胺瞬变，其次是对与整个幼仔分开的选定幼崽线索的反应。总之，这些实验的结果将（1）确定特定的幼崽相关刺激、正常母体行为和多巴胺瞬变之间的关系，以及（2）验证妊娠期可卡因的使用如何改变母婴二人组中的这些关系。这些研究的数据将为未来关于孕产妇行为中阶段性多巴胺信号的因果关系和生化基础以及慢性可卡因对其失调的研究奠定坚实的基础，并将帮助我们了解人类对吸毒母亲的忽视。