Insel T R, Winslow J T, Wang Z X, Young L, Hulihan T J
Dept. of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30322, USA.
Adv Exp Med Biol. 1995;395:227-34.
Previous studies in rats have implicated central oxytocin (OT) pathways in the onset of maternal behavior, female sexual receptivity, and the response of the pups to social separation. However, the rat is not ideal for studying effects of OT on attachment as rats fail to form selective, enduring social bonds. To study male-female pair bonds, our laboratory has focused on a microtine rodent, the prairie vole, which is monogamous and highly affiliative. Adult prairie voles form pair bonds after mating (with prolonged, repeated bouts of copulation). As mating releases OT in several species of mammals, we hypothesized that this release was important for pair bond formation in the prairie vole. Central administration of an OT antagonist (but not a V1 antagonist) prevents pair bonding without interfering with the mating behavior. Moreover, central infusion of OT (but not vasopressin, AVP) facilitates pair bonding n the absence of mating. In males, it is AVP (not OT) that appears necessary for pair bond formation. The pattern of OT (and AVP) receptor distribution in the prairie vole brain is entirely distinct from the pattern observed in the closely related non-monogamous montane vole. OT receptors (OTR) in these two species show virtually identical kinetics, specificities, and cDNA sequences (RNA from parturient uterus). In current studies, we are screening genomic libraries from prairie and montane voles to determine if species differences in OTR promoters account for the strikingly different patterns of regional expression in brain. These studies should ultimately provide insight into a neuroendocrine mechanism for pair bond formation.
先前对大鼠的研究表明,中枢催产素(OT)通路与母性行为的启动、雌性性接受能力以及幼崽对社会隔离的反应有关。然而,大鼠并非研究OT对依恋影响的理想动物,因为大鼠无法形成选择性的、持久的社会联系。为了研究雌雄配对关系,我们实验室聚焦于一种小型啮齿动物——草原田鼠,它是一夫一妻制且高度亲和的。成年草原田鼠在交配后(经过长时间、反复的交配回合)形成配对关系。由于交配会在几种哺乳动物中释放OT,我们推测这种释放对草原田鼠的配对关系形成很重要。中枢给予OT拮抗剂(而非V1拮抗剂)可阻止配对关系的形成,且不干扰交配行为。此外,在没有交配的情况下,中枢注入OT(而非加压素,AVP)可促进配对关系的形成。在雄性中,似乎是AVP(而非OT)对配对关系的形成是必需的。草原田鼠大脑中OT(和AVP)受体的分布模式与在亲缘关系相近的非一夫一妻制山地田鼠中观察到的模式完全不同。这两个物种中的OT受体(OTR)在动力学、特异性和cDNA序列(来自分娩子宫的RNA)方面几乎相同。在当前的研究中,我们正在筛选草原田鼠和山地田鼠的基因组文库,以确定OTR启动子的物种差异是否可解释大脑中区域表达的显著不同模式。这些研究最终应能深入了解配对关系形成的神经内分泌机制。