Dopamine Regulation of Social Attachment

描述（由申请人提供）：尽管社会依恋的神经生物学与精神病学、心理学和发展心理生物学相关，但它仍然相对未被研究。最近对草原田鼠（Microtus ochrogaster）这一一夫一妻制啮齿动物的研究，为社会依恋的定量研究提供了可靠的行为指标。草原田鼠表现出交配诱导的配对关系，这表明它们对配偶的持续偏好比对同种陌生人的偏好（伴侣偏好）更大。先前的研究已经证明了多巴胺（DA）在这一过程中的作用。DA在交配过程中在伏隔核（NAcc）中释放，DA作用于NAcc壳中的d2型受体，促进伴侣偏好的形成，Dl型和d2型受体对配对的调节相反。此外，NAcc中的神经肽催产素（OT）也参与了配对结合的调节。尽管这些数据揭示了NAcc、DA和OT在配对键形成中的重要性，但对DA和OT在配对键形成中的细胞内机制和相互作用知之甚少。在本研究中，我们提出了四项研究，旨在系统地研究cAMP第二信使级联以及DA和OT在NAcc中的相互作用在雄性草原田鼠配对结合中的作用。在Specific Aim 1中，我们将研究在草原田鼠的NAcc中，在交配和配对键形成以及D2型受体激活过程中cAMP级联的活性。在Specific Aim 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对成对键和cAMP活性的作用。在Specific Aim 4中，我们将研究DA和OT在NAcc中的相互作用对伴侣偏好形成和cAMP级联活性的影响。总之，这些研究应该提供了一个全面的理解细胞内的cAMP级联在NAcc的DA-OT相互作用下对配对键的调节。这些研究的成功完成将极大地促进我们对社会依恋的神经生物学的理解，从而为与人类无法形成社会联系相关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.