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）：在人类和动物研究中充分记录了孕产妇对婴儿的滥用造成较高水平的孕产妇行为，而相关的神经机制尚不清楚。几项啮齿动物研究表明，与非卡通暴露的母亲相比，与可卡因暴露的母亲女性相比，可能会少于幼崽。一种可能性是，已知可以促进正常母亲的母亲反应的幼犬刺激被认为是暴露于可卡因的母亲的动机较少。动机行为是通过中辅助途径中多巴胺活性调节的。腹侧纹状体中的快速多巴胺释放事件，即多巴胺瞬变，是在检测显着刺激时发生的奖励预测的神经信号，通常是在加固的方法之前。我们假设大鼠母亲的多巴胺瞬变是由幼犬刺激引起的，并促进了正常的幼崽指导的孕产妇行为，而可卡因治疗的母亲则使DA释放到刺激的刺激中，从幼犬中刺激，与较少的母体反应相关，并由孕产妇组合驱动。可卡因的多巴胺改变和可卡因暴露的幼犬产生的刺激改变。我们建议使用快速扫描循环伏安法以在既定的孕产妇行为模型中测量多巴胺释放。因此，我们将确定怀孕期间的母体可卡因暴露是否减少了幼犬指导的行为，也会减少母体多巴胺释放到幼犬提示。我们将使用一种两步的方法：我们将首先在啮齿动物母亲中介绍多巴胺瞬变，因为他们对垃圾做出响应，其次是与整个垃圾分别响应选定的幼犬提示。总之，这些实验的结果将（1）确定特定幼崽相关的刺激，正常的母体行为和多巴胺瞬变之间的关系，以及（2）验证妊娠可卡因的使用如何改变母亲二元的这些关系。这些研究的数据将为未来的研究提供扎实的基础，该研究涉及孕产妇行为中阶段性多巴胺信号的因果关系和生化基础，以及慢性可卡因的失调，并将告知我们对人类对吸毒母亲的孕产妇忽视的理解。