Joint contributions of affiliative social contact, stress in adolescence and oxytocin to fear behaviour in adult rats

恐惧也许是我们最原始的情感。适当的恐惧水平产生适应性防御反应，促进生存。过度的恐惧反应可能是适应不良的。我感兴趣的是恐惧表达的神经调节，以及这个过程是如何被先前的经验塑造的。在婴儿期和/或幼儿期经历压力，在某些情况下，可以增强（而不是阻碍）以后生活的恢复力。我想知道，由经验引起的韧性的增加是否也可以在青春期开始。我们最近的研究结果表明，获得亲和的社会接触可能会将青少年压力的持久结果转向增强的弹性，这一点可以通过成年后较低水平的恐惧表达来证明。我们现在想扩展这些发现。我们将在青春期早期或中期将单个和成对圈养的雄性和雌性大鼠暴露于间歇性身体压力（IPS），然后测试它们对成年期急性威胁的行为反应。我们预计，在青春期有IPS病史的成对圈养大鼠相对于无压力/成对圈养对照大鼠将显示出较低水平的行为恐惧，而在单圈养/IPS大鼠中则相反。其他实验将探讨神经肽，催产素（OT）在经验诱导的弹性的潜在参与。这包括通过我们的青少年压力协议（如上所述）处理大鼠，然后用OT标记物标记它们的成年脑组织。我们预计，成对圈养/IPS大鼠将显示最高数量的OT阳性细胞在下丘脑地区丰富的OT-生产细胞。这些相同的大鼠还将在涉及防御行为的两个相互连接的大脑区域（外侧隔（LS）和前下丘脑（AHA））中显示最高密度的OT阳性纤维。为了进一步探索OT在减少恐惧中的作用，我们将使青春期有IPS病史的单身和成对饲养的大鼠暴露于急性威胁，即成年后的电击探针掩埋试验（SPBT）。SPBT后，我们将通过处理其脑组织，使用神经元活性标记物cFos和OT的抗体进行双重免疫标记，评估OT产生细胞的威胁诱导激活。我们预计，对圈养/IPS大鼠将显示最低水平的恐惧表达的SPBT，这将与最高数量的双标记细胞在下丘脑。一系列实验旨在确定将OT直接注入LS或AHA是否会减少大鼠在各种行为测试中的恐惧表达。这项研究将提供有关因素（亲和性社会接触，逆境年龄，性别，催产素）的新信息，这些因素可能相互作用，以塑造青春期逆境的持久结果，从而在以后的生活中对不良事件具有更大的敏感性或弹性。最终，研究结果可能会为旨在支持加拿大弱势青年的努力提供信息。

Fear is perhaps our most primal emotion. Appropriate levels of fear yield adaptive defensive responses that promote survival. Excessive fear reactions can be maladaptive. I am interested in the neural regulation of fear expression and how this process is shaped by prior experience. Experiencing stress in infancy and/or early childhood can, in certain instances, enhance (rather than impede) resilience in later life. I want to know if experience-induced increases in resilience can also be initiated in adolescence. Our recent findings suggest that access to affiliative social contact might shift the lasting outcomes of adolescent stress toward enhanced resilience, as evidenced by lower levels of fear expression in adulthood. We now want to extend those findings. We will expose single and pair-housed, male and female rats to intermittent physical stress (IPS) in early or mid-adolescence and then test their behavioural responses to acute threats in adulthood. We expect that pair-housed rats with a history of IPS in adolescence will display lower levels of behavioural fearfulness relative to no-stress/pair-housed control rats, whereas the reverse will be found in single-housed/IPS rats. Additional experiments will explore the potential involvement of the neuropeptide, oxytocin (OT) in experience-induced resilience. This involves processing rats through our adolescent stress protocol (as described above) and then labelling their adult brain tissue with a marker for OT. We expect that pair-housed/IPS rats will display the highest number of OT positive cells in hypothalamic areas rich in OT-producing cells. These same rats will also display the highest density of OT positive fibers in two interconnected brain regions implicated in defensive behaviour, the lateral septum (LS) and anterior hypothalamus (AHA). To further explore the involvement of OT in fear reduction, we will expose single and pair-housed rats with a history of IPS in adolescence to an acute threat, the shock-probe burying test (SPBT) in adulthood. After the SPBT, we will evaluate threat-induced activation of OT-producing cells by processing their brain tissue for double immuno-labelling using antibodies for the neuronal activity marker, cFos and OT. We expect that pair-housed/IPS rats will display the lowest levels of fear expression in the SPBT, and this will be associated with the highest number of double labelled cells in the hypothalamus. A complimentary series of experiments aims to determine whether infusing OT directly into the LS or AHA reduces rats' fear expression in various behavioural tests. This research will provide novel information about factors (affiliative social contact, age at adversity, sex, oxytocin) that potentially interact to shape the lasting outcomes of adversity in adolescence, thus conferring either greater sensitivity or resilience to adverse events in later life. Ultimately, the findings might inform endeavors aimed at supporting vulnerable youth in Canada.