Dopamine Regulates Drug and Social Reward Interactions

多巴胺调节药物和社会奖励相互作用

• 批准号: 7668595
• 负责人: ZUOXIN WANG
• 金额: $ 11.48万
• 依托单位: FLORIDA STATE 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/7668595
• 关键词: Address; Adult; Amphetamines; Animal Model; Behavior; Behavioral; Cyclic AMP; Dopamine; Dopamine Receptor; Dose; Drug Addiction; Drug abuse; Eating; Female; Future; Generations; Human; Intervention; Investigation; Laboratory Rat; Learning; Mammals; Mediating; Microtus; Modeling; Mus; Nature; Neurobiology; Nucleus Accumbens; Pair Bond; Partner in relationship; Pharmaceutical Preparations; Play; Prevention; Process; Regulation; Research; Research Technics; Rewards; Rodent; Rodent Model; Role; Sex Characteristics; Social Environment; Social Interaction; Study models; Testing; Time; addiction; behavioral sensitization; drug of abuse; drug reward; experience; fitness; innovation; male; neural circuit; neuromechanism; novel; prairie vole; preference; receptor expression; response; reward processing; sex; social; social attachment; tool; transmission process

DESCRIPTION (provided by applicant): It is believed that drugs of abuse usurp neural circuitry that initially evolved to mediate behavioral processes essential for fitness. Therefore, the take over of this circuitry by drugs of abuse usually exerts powerful control over the behavior and this is a tremendous problem for many humans. One important factor contributing to drug abuse is social environment. It has been suggested that social attachments formed in adulthood may have significant impact on drug addictions. Unfortunately, investigation into this topic is very limited partially because the vast majority of addiction research is conducted on traditional laboratory rats and mice that do not form adult-adult social attachments. Here we propose a novel line of research using a unique animal model to address fundamental questions regarding the interaction of social and drug reward and the underlying neural mechanisms. The monogamous prairie vole (Microtus ochrogaster) displays mating-induced pair bonding between mates, and this behavior is mediated by dopamine (DA) in the nucleus accumbens (NAcc). Recently, we also found that the prairie vole displays amphetamine (AMPH)-induced conditioned place preference (CPP) and DA is involved in this behavior. As natural reward and maladaptive drug reward are both regulated by DA, we hypothesized that these overlapping neural mechanisms will result in behavioral and neurobiological interactions between pair bonding and drug addiction. Here, we propose four studies by taking advantage of the vole model to systematically address interactions between pair bonding and drug reward and to study NAcc DA involvement in the regulation of such interactions. Aim 1 will firmly establish the prairie vole model for drug reward by performing detailed dose response curves for AMPH-induced CPP and behavioral sensitization. Aim 2 will examine NAcc DA involvement in AMPH reward. Aim 3 will study behavioral interactions between pair bonding and AMPH reward. Aim 4 will investigate the role of NAcc DA in the regulation of interactions between pair bonding and AMPH reward. Successful completion of these studies will further our understanding of behavioral and neurobiological interactions between social and drug reward, and such findings will have the potential to facilitate behavioral and neuropharmacological interventions that may aid addiction prevention. Further, this research will provide an opportunity for me to learn new research techniques and to devote more time on developing a new research paradigm important for the study of neurobiology of drug and social reward interactions.

描述(申请人提供)：人们认为滥用药物会篡夺神经回路，而神经回路最初进化为调节对健康至关重要的行为过程。因此，滥用药物接管这一回路通常会对行为施加强大的控制，这对许多人来说是一个巨大的问题。造成药物滥用的一个重要因素是社会环境。有人认为，成年后形成的社会依恋可能对吸毒成瘾有重大影响。不幸的是，对这一主题的调查非常有限，部分原因是绝大多数成瘾研究是在传统的实验室大鼠和小鼠上进行的，这些大鼠和小鼠没有形成成人与成人之间的社交依恋。在这里，我们提出了一种新的研究路线，使用一个独特的动物模型来解决关于社会和药物奖励的相互作用以及潜在的神经机制的基本问题。一夫一妻制草原田鼠(Microtus Ochrogaster)在配偶之间表现出交配诱导的配对结合，这种行为是由伏核(NAcc)中的多巴胺(DA)介导的。最近，我们还发现草原田鼠表现出苯丙胺(Amph)诱导的条件性位置偏爱(CPP)，DA参与了这一行为。由于自然奖赏和不适应的药物奖赏都由DA调节，我们假设这些重叠的神经机制将导致配对结合和药物成瘾之间的行为和神经生物学相互作用。在这里，我们提出了四项研究，利用VOLE模型系统地研究了配对结合和药物奖励之间的相互作用，并研究了NAcc DA参与这种相互作用的调节。目的1通过绘制AMPH诱导的CPP和行为敏化的详细剂量反应曲线，建立草原田鼠药物奖赏模型。目标2将审查NAcc DA在AMPH奖励中的参与。目标3将研究配对结合和AMPH奖励之间的行为交互作用。目的4将研究NAcc DA在配对结合和Amph奖励之间相互作用的调节中的作用。这些研究的成功完成将进一步加深我们对社会奖励和药物奖励之间的行为和神经生物学相互作用的理解，这些发现将有可能促进有助于成瘾预防的行为和神经药物干预。此外，这项研究将为我提供一个学习新的研究技术的机会，并将更多的时间投入到开发一种新的研究范式上，这对研究药物和社会奖励相互作用的神经生物学很重要。