Nucleus Accumbens Dopamine and Social Attachment

描述（由申请人提供）：多巴胺涉及与社会缺陷相关的人类疾病，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的社会关系，我们知之甚少。草原田鼠是研究社会关系的理想动物模型，因为雄性和雌性形成长期的伴侣关系。伴侣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，在测试中，受试者倾向于花更多的时间与熟悉的伴侣在一起，而不是与相同的陌生人在一起。这一提议将验证一种假设，即交配过程中释放的多巴胺促进了交配引起的伴侣偏好。我的初步实验表明，非特异性多巴胺受体拮抗剂（通过体外注射或微注射到伏隔核中）阻断了交配诱导的伴侣偏好，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纵伴侣偏好形成，来确定伏隔核中对配对结合很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起作用来影响配对，所以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，我将检验交配是否会增加伏隔核的多巴胺释放。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.