Dopamine Regulates Drug and Social Reward Interactions

描述（由申请人提供）：人们认为滥用药物篡夺了神经回路，而神经回路最初是为了调节健康所必需的行为过程而进化的。因此，滥用药物接管这个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，成年期形成的社会依恋可能对药物成瘾有重大影响。不幸的是，对这个话题的调查非常有限，部分原因是绝大多数成瘾研究都是在传统的实验室大鼠和小鼠身上进行的，这些大鼠和小鼠没有形成成年社会依恋。在这里，我们提出了一个新的研究路线，使用一个独特的动物模型来解决有关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）表现出交配诱导的交配行为，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）诱导的条件位置偏好（CPP），而DA参与了这一行为。由于自然奖励和不良药物奖励都受到DA的调节，我们假设这些重叠的神经机制将导致配对结合与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研究配对结合和药物奖励之间的相互作用，并研究NAcc - DA参与这种相互作用的调节。Aim 1将通过详细的amph诱导CPP和行为致敏的剂量反应曲线，建立草原田鼠药物奖励模型。目的2将检查NAcc DA参与AMPH奖励。目的3将研究配对结合与AMPH奖励之间的行为相互作用。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，可能有助于成瘾预防。此外，这项研究将为我提供一个学习新的研究技术的机会，并投入更多的时间来开发一个新的研究范式，这对药物和社会奖励相互作用的神经生物学研究很重要。

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.