Neurobiological Mechanisms of Social Bonding in a Monogamous Primate

描述（由申请人提供）：本研究的主要目标是利用一种独特的非人类灵长类动物模型，进一步了解社会联系的神经生物学基础。社会联系功能障碍是许多发育障碍和精神障碍的基础，并对身心健康产生长期影响。在这个更广泛的背景下，我们建议研究一种表现出高水平选择性社会联系的物种，即一夫一妻制的山雀猴（Callicebus cupreus）。这个物种表现出一种成对结合，或雄性和雌性之间的选择性依恋，以及后代对父亲的依恋。非人类灵长类动物模型是啮齿动物模型的一个有价值的补充，因为它们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，因为对个人经验和实验条件有更大的控制。精氨酸抗利尿激素（AVP）和催产素（OT）是已知的与啮齿动物的社会关系有关的神经肽激素。虽然也有证据表明它们在灵长类动物的社会联系中起着作用，但这个过程的方向性尚不清楚。我们建议区分AVP、OT和社会联系之间的三种关系模型：a)成熟-在一夫一妻制物种中，社会联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）建立了形成配对关系的倾向；b)情境- AVP和OT系统的变化完全是环境的，是成对关系或父母依恋形成的直接结果。在这个模型中，这些变化在失去依恋后是可逆的，并且c)结合——AVP和/或OT的不可逆的成熟变化为成人依恋的形成奠定了基础，成对结合的形成随后引起进一步的变化，而依恋的丧失可以“重置”这一过程。我们之前对该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（依恋纽带形成和破坏的肾上腺皮质反应，Mendoza等人，2000）的证据。我们对当前研究的总体假设是，这两个过程与神经肽对配对键合的调节相结合-提出的“组合”模型。公共卫生相关性：在这里，我们建议在一种非人类灵长类动物模型中研究催产素和抗利尿激素与社会纽带发展之间的关系。这与自闭症等社会联系障碍的研究有关。

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.