Nucleus Accumbens Dopamine and Social Attachment

描述(申请人提供)：多巴胺与人类与社会缺陷有关的疾病有关，如自闭症，多巴胺能药物经常用于治疗这些疾病的症状。然而，关于多巴胺如何调节哺乳动物之间的社会联系，人们知之甚少。草原田鼠是社会联系神经生物学研究的理想动物模型，因为雄性和雌性形成长期的配对纽带。伴侣偏好测试是对伴侣关系的评估，这是一种可靠的行为指标，受试者与熟悉的伴侣在一起的时间比与同种陌生人相处的时间更多。这项提议将检验这样一种假设，即交配过程中释放的多巴胺促进了交配诱导的伴侣偏好。我的初步实验表明，一种非特异性的多巴胺受体拮抗剂(无论是I.P.或微量注射入伏隔核)阻断了交配诱导的配偶偏好，而非特异性多巴胺受体激动剂在没有交配的情况下诱导了这种行为。我建议通过使用受体特异性药物来操控伴侣偏好的形成，来识别伏核中对配对结合至关重要的多巴胺受体亚型。由于多巴胺不太可能只在一个中心位置影响配对结合，因此我将绘制雄性草原田鼠的多巴胺系统图，并测试交配是否会改变多巴胺系统。最后，我将研究交配是否会增加伏隔核多巴胺的释放。总之，这些研究将进一步加深我们对多巴胺如何参与哺乳动物社交依恋的理解。

DESCRIPTION (provided by applicant): Dopamine is implicated in human diseases associated with social deficits, such as autism, and dopaminergic drugs are frequently used to treat symptoms of these diseases. However, very little is known about how dopamine may regulate social affiliation among mammals. The prairie vole is an ideal animal model for the neurobiological investigation of social affiliation because males and females form long-term pair bonds. Pair bonding is assessed by the partner preference test, a reliable behavioral index in which the subject spends preferentially more time with its familiar mate versus a conspecific stranger. This proposal will test the hypothesis that mating induced partner preferences are facilitated by dopamine released during mating. My preliminary experiments show that a non-specific dopamine receptor antagonist (either i.p. or microinjected into nucleus accumbens) blocked mating-induced partner preferences and a non-specific dopamine receptor agonist induced this behavior in the absence of mating. I propose to identify the dopamine receptor subtype in the nucleus accumbens that is important for pair bonding by using receptor specific drugs to manipulate partner preference formation. Since it is unlikely that dopamine acts at only one central location to influence pair bonding, I will then map the dopamine system in the male prairie vole and test if mating alters dopamine systems. Finally, I will examine if mating increases dopamine release in the nucleus accumbens. Together these studies will further our understanding of how dopamine is involved in mammalian social attachment.