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。

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 pre-treatment of the DA receptor antagonist blocked 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. In Specific Aim 1, we will firmly establish the vole model for drug reward by performing detailed dose response curves for AMPH induced CPP and behavioral sensitization. In Specific Aim 2, we will examine NAcc DA involvement in AMPH reward. In Specific Aim 3, we will study behavioral interactions between pair bonding and AMPH reward. In Specific Aim 4, we 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.