Neurobiological Mechanisms of Social Bonding in a Monogamous Primate

描述(由申请人提供)：这项研究的主要目标是通过使用一个独特的非人类灵长类动物模型来加深我们对社会联系的神经生物学基础的理解。社会联系障碍是许多发育和精神障碍的基础，并对身心健康产生长期后果。在这个更广泛的背景下，我们建议研究一种表现出高度选择性社会纽带的物种--一夫一妻制的Titi猴子(Callicebus Cupreus)。该物种表现出雄性和雌性之间的结对结合或选择性依恋，以及后代对其父亲的依恋。非人灵长类动物模型是啮齿动物模型的一个有价值的补充，因为它在神经解剖学上更接近人类。在许多情况下，它们也比直接研究人类更可取，因为它们可以更好地控制个人经验和实验条件。精氨酸加压素(AVP)和催产素(OT)是已知的参与啮齿动物社会纽带的神经肽激素。尽管也有证据表明它们在灵长类动物的社会关系中发挥了作用，但这一过程的方向性尚不清楚。我们建议区分AVP、OT和社会关系的三种模式：a)成熟--一夫一妻制物种中社会关系的形成是不可逆的、与年龄相关的成熟过程的结果，在这个过程中，AVP和OT系统的变化(合成增加，受体结合的变化)建立了形成双键的倾向；b)AVP和OT系统的情景变化完全是环境的，是形成双键或亲本依恋的直接结果。在这个模型中，这些变化是可逆的，一旦失去依恋图形，以及c)结合--虽然AVP和/或OT不可逆转的成熟变化为成人依恋的形成奠定了基础，但成对键的形成随后会导致进一步的变化，而依恋图形的丢失可以重新启动这一过程。我们以前对这一物种的研究显示了成熟变化(性腺激素，Valeggia等人，1999)和情境变化(肾上腺皮质对连接键的形成和中断的反应，Mdoza等人，2000)的证据。我们对当前研究的主要假设是，这两个过程是结合在一起的，涉及神经肽对结合的调节--所提出的“结合”模型。公共卫生相关性：在这里，我们建议研究荷尔蒙催产素和后叶加压素之间的关系，以及在非人类灵长类动物模型-铜蒂猴中社会纽带的发展。这与自闭症等社会纽带障碍的研究有关。

DESCRIPTION (provided by applicant): The primary goal of this research is to further our understanding of the neurobiological basis of social bonding, using a unique non-human primate model. Dysfunctions in social bonding underlie a number of developmental and psychiatric disorders, as well as having long-term consequences for physical and psychological health. In this broader context, we propose to study a species which displays high levels of selective social bonding, the monogamous titi monkey (Callicebus cupreus). This species displays a pair-bond, or selective attachment between males and females, as well as attachment by offspring to their father. Non-human primate models are a valuable addition to rodent models, in being neuroanatomically much closer to humans. In many cases they are also preferable to studying humans directly, because of the greater control possible over individual experience and experimental conditions. Arginine vasopressin (AVP) and oxytocin (OT) are neuropeptide hormones known to be involved in social bonding in rodents. Although there is also evidence for their role in primate social bonding, the directionality of the process is unclear. We propose to distinguish between three models of the relationship between AVP, OT and social bonding: a) Maturational - the formation of social bonds in a monogamous species are the results of irreversible, age-related maturational processes in which changes in the AVP and OT systems (increases in synthesis, changes in receptor binding) set up a predisposition to form a pair-bond; b) Situational - changes in the AVP and OT systems are completely environmental and the direct result of the formation of a pair-bond or parental attachment. In this model, these changes are reversible upon the loss of the attachment figure, and c) Combination - while irreversible maturational changes in AVP and/or OT set the stage for formation of an adult attachment, the formation of a pair-bond then induces further changes and the loss of an attachment figure can "reset" the process. Our previous research in this species shows evidence for both maturational changes (gonadal hormones, Valeggia et al., 1999) and situational changes (adrenocortical response to formation and disruption of attachment bonds, Mendoza et al., 2000). Our overarching hypothesis for the current research is that both processes are combined with respect to neuropeptide regulation of pair-bonding - the proposed "combination" model. PUBLIC HEALTH RELEVANCE: Here we propose to study the relationship between the hormones oxytocin and vasopressin, and the development of social bonding in a non-human primate model, the coppery titi monkey. This is relevant to the study of disorders of social bonding such as autism.