Dopamine Regulation of Social Attachment

多巴胺对社会依恋的调节

• 批准号: 8031040
• 负责人: ZUOXIN WANG
• 金额: $ 10.17万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8031040
• 关键词: Address; Aggressive behavior; Animal Model; Area; Behavior; Behavioral; Biological Models; Brain; Cyclic AMP; Cyclic AMP-Responsive DNA-Binding Protein; Data; Development; Disease; Dopamine; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor; Dopamine Receptor; Event; Exhibits; Female; GTP-Binding Proteins; Human; Immediate-Early Genes; Laboratories; Measures; Memory; Microtinae; Microtus; Molecular; Motivation; Neurobiology; Neuropeptides; Neurosciences; Nucleus Accumbens; Oxytocin; Oxytocin Receptor; Pair Bond; Partner in relationship; Phosphorylation; Process; Proteins; Psychiatry; Psychology; Psychopathology; Receptor Activation; Regulation; Research; Research Personnel; Rodent; Role; Second Messenger Systems; Sensory Process; Signal Pathway; Signal Transduction; Social Behavior; System; Testing; base; design; developmental psychobiology; extracellular; field study; indexing; male; neural circuit; neurochemistry; prairie vole; preference; programs; receptor; relating to nervous system; second messenger; sex; social attachment; social separation

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.

描述（由申请人提供）：尽管与精神病学，心理学和发展心理生物学相关，但社会依恋的神经生物学仍然相对未经评价。最近对一夫一妻制的啮齿动物（Microtus ochrogaster）的研究为社会依恋定量研究提供了可靠的行为指数。草原田鼠表现出交配诱导的配对键合，这表明了伴侣与特定陌生人（伴侣偏爱）的持续偏好。先前的研究证明了多巴胺（DA）在此过程中的作用。 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，以促进伴侣的偏好形成，而DL-和D2-Type受体的调制相反。此外，NaCC中的神经肽催产素（OT）也与配对键的调节有关。尽管这些数据揭示了NACC DA和OT在成对键形成中的重要性，但对DA和OT基础配对键的细胞内机理和相互作用知之甚少。在本应用中，我们提出了四项研究，以系统地研究CAMP第二信使级联的作用以及DA和OT在NACC中的相互作用在雄性草原田鼠中的配对键调节中的相互作用。在特定的目标1中，我们将检查cAMP级联反应在交配过程中的活性和配对键形成以及在草原Vole的NACC中的D2-型受体激活期间。在特定的目标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。在特定的目标3中，我们将确定NACC OT在配对键和营地活动中的作用。在特定的目标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级联活动的影响。总之，这些研究应为NACC中的基本cAMP级联反作用在配对键的调节中提供全面的理解。这些研究的成功完成将大大进一步了解我们对社会依恋神经生物学的理解，因此提供了有关与无法形成人类社会纽带相关的疾病的有价值的信息。