Dopamine Regulation of Social Attachment

描述（由申请人提供）：社会依恋的神经生物学仍然相对未被研究，尽管它与精神病学，心理学和发展心理生物学有关。最近的研究与一夫一妻制的啮齿动物，草原田鼠（Microtus ochrogaster），提供了一个可靠的行为指标的定量研究的社会依恋。草原田鼠表现出交配诱导的配对键合，这是由一个持续的偏好的伴侣与同种陌生人（合作伙伴偏好）。以前的研究已经证明了多巴胺（DA）在这一过程中的作用。在交配过程中，DA被释放到丘脑核（NAcc）中，DA作用于NAcc壳中的D2型受体以促进伴侣偏好的形成，并且D1和D2型受体对配对键合具有相反的调节。此外，NAcc中的神经肽催产素（OT）也参与了对键合的调节。虽然这些数据揭示了NAcc DA和OT在成对键形成中的重要性，但对DA和OT潜在的成对键形成的细胞内机制和相互作用知之甚少。在本申请中，我们提出了四项研究，系统地调查的作用，cAMP的第二信使级联和相互作用的DA和OT在NAcc在调节配对成键的雄性草原田鼠。在具体目标1中，我们将研究在交配和成对键形成过程中以及在草原田鼠的NAcc中D2型受体激活过程中cAMP级联的活性。在具体目标2中，我们将研究NAcc中G蛋白/ cAMP操纵对伴侣偏好形成的影响。在具体目标3中，我们将确定NAcc OT对成对键合和cAMP活性的作用。在具体目标4中，我们将研究NAcc中DA和OT相互作用对伴侣偏好形成和cAMP级联活性的影响。总之，这些研究应该提供一个全面的了解细胞内cAMP级联的基础DA-OT相互作用在NAcc的调节对键合。这些研究的成功完成将大大加深我们对社会依恋的神经生物学的理解，从而为人类无法形成社会联系的疾病提供有价值的信息。

DESCRIPTION (provided by applicant): The neurobiology of social attachment remains relatively uninvestigated despite its relevance to psychiatry, psychology, and developmental psychobiology. Recent studies with a monogamous rodent, the prairie vole (Microtus ochrogaster), have provided a reliable behavioral index for quantitative studies of social attachment. Prairie voles exhibit mating-induced pair bonding which is indicated by a sustained preference for a mate versus a conspecific stranger (partner preference). Previous research has demonstrated the role of dopamine (DA) in this process. DA is released in the nucleus accumbens (NAcc) during mating, DA acts on D2-type receptors in the NAcc shell to facilitate partner preference formation, and Dl- and D2-type receptors have opposite modulation of pair bonding. In addition, neuropeptide oxytocin (OT) in NAcc has also been implicated in the regulation of pair bonding. Although these data reveal the importance of NAcc DA and OT in pair bond formation, little is known about the intracellular mechanisms and interactions of DA and OT underlying pair bonding. In the present application, we propose four studies to systematically investigate the role of the cAMP second messenger cascade and interactions of DA and OT in NAcc in the regulation of pair bonding in male prairie voles. In Specific Aim 1, we will examine the activity of the cAMP cascade during mating and pair bond formation as well as during D2- type receptor activation in the prairie vole's NAcc. In Specific Aim 2, we will investigate the effects of the G protein/ cAMP manipulation in NAcc on partner preference formation. In Specific Aim 3, we will determine the role of NAcc OT on pair bonding and on the cAMP activity. In Specific Aim 4, we will investigate the effects of DA and OT interactions in NAcc on partner preference formation and on the cAMP cascade activity. Together, these studies should provide a comprehensive understanding of the intracellular cAMP cascade underlying DA-OT interactions in NAcc in the regulation of pair bonding. Successful completion of these studies will significantly further our understanding of neurobiology of social attachment and therefore provide valuable information regarding disorders associated with inability to form social bonds in humans.