Dopamine Regulates Drug and Social Reward Interactions

多巴胺调节药物和社会奖励相互作用

基本信息

批准号：
8116516
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
项目类别：
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

项目摘要

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（由申请人提供）：据信滥用药物会侵占最初进化为调节健身所必需的行为过程的神经回路。因此，滥用药物接管该回路通常会对行为产生强大的控制，这对许多人来说是一个巨大的问题。社会环境是导致药物滥用的重要因素之一。有人认为，成年后形成的社会依恋可能对毒瘾产生重大影响。不幸的是，对这个主题的研究非常有限，部分原因是绝大多数成瘾研究是在不形成成年社会依恋的传统实验室大鼠和小鼠上进行的。在这里，我们提出了一种新颖的研究路线，使用独特的动物模型来解决有关社会和药物奖励相互作用以及潜在神经机制的基本问题。一夫一妻制的草原田鼠（Microtus ochrogaster）在配偶之间表现出交配诱导的配对结合，这种行为是由伏隔核（NAcc）中的多巴胺（DA）介导的。最近，我们还发现草原田鼠表现出安非他明（AMPH）诱导的条件性位置偏好（CPP），而DA参与了这种行为。由于自然奖励和适应不良药物奖励均受 DA 调节，我们假设这些重叠的神经机制将导致配对关系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，利用田鼠模型来系统地解决配对关系和药物奖励之间的相互作用，并研究 NAcc DA 参与此类相互作用的调节。目标 1 将通过对 AMPH 诱导的 CPP 和行为致敏进行详细的剂量反应曲线，牢固地建立药物奖励的草原田鼠模型。目标 2 将检查 NAcc DA 参与 AMPH 奖励。目标 3 将研究结对关系和 AMPH 奖励之间的行为相互作用。目标 4 将研究 NAcc DA 在调节配对结合和 AMPH 奖励之间相互作用中的作用。这些研究的成功完成将进一步我们对社会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行为和神经药理学干预，从而有助于预防成瘾。此外，这项研究将为我提供一个学习新研究技术的机会，并投入更多时间来开发对于药物和社会奖励相互作用的神经生物学研究很重要的新研究范式。