Nucleus Accumbens Dopamine and Social Attachment

说明（由申请人提供）：多巴胺与人类社会缺陷相关疾病有关，如自闭症，多巴胺能药物常用于治疗这些疾病的症状。 然而，人们对多巴胺如何调节哺乳动物之间的社会关系知之甚少。草原田鼠是一种理想的动物模型，为神经生物学研究的社会联系，因为男性和女性形成长期的配对债券。配对关系是通过伴侣偏好测试来评估的，这是一个可靠的行为指标，在这个指标中，受试者优先与熟悉的伴侣而不是同种陌生人呆在一起。这项建议将测试的假设，交配诱导的合作伙伴的喜好，促进了多巴胺在交配过程中释放。我的初步实验表明，一种非特异性多巴胺受体拮抗剂（无论是腹腔注射还是显微注射到丘脑核）阻断了交配诱导的伴侣偏好，而一种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。我建议确定多巴胺受体亚型的神经核，这是重要的配对键合，通过使用受体特异性药物来操纵伴侣偏好的形成。由于多巴胺不太可能只在一个中心位置起作用来影响配对，我将绘制雄性草原田鼠的多巴胺系统，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丘脑核中多巴胺的释放。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会依恋的理解。

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.