Ryabinin Andrey, Johnson Michael, Zweig Jonathan, Zhang Yangmiao, Nunez Louis, Ryabinina Olga, Hibert Marcel
Oregon Health & Science University.
CNRS / Université de Strasbourg.
Res Sq. 2024 May 15:rs.3.rs-4351761. doi: 10.21203/rs.3.rs-4351761/v1.
There is much interest in targeting the activity in the oxytocin system to regulate social bonding. However, studies with exogenous administration of oxytocin face the caveats of its low stability, poor brain permeability and insufficient receptor specificity. The use of a small-molecule oxytocin receptor-specific agonist could overcome these caveats. Prior to testing the potential effects of a brain-penetrant oxytocin receptor agonist in clinical settings, it is important to assess how such an agonist would affect social bonds in animal models. The facultatively monogamous prairie voles (), capable of forming long-term social attachments between adult individuals, are an ideal rodent model for such testing. Therefore, in a series of experiments we investigated the effects of the recently developed oxytocin receptor-specific agonist LIT-001 on the acquisition and expression of partner preference, a well-established model of pair bonding, in prairie voles. LIT-001 (10 mg/kg, intraperitoneal), as expected, facilitated the acquisition of partner preference when administered prior to a 4-hour cohabitation. In contrast, while animals injected with vehicle after the 4-hour cohabitation exhibited significant partner preference, animals that were injected with LIT-001 did not show such partner preference. This result suggests that OXTR activation during expression of pair bonding can inhibit partner preference. The difference in effects of LIT-001 on acquisition versus expression was not due to basal differences in partner preference between the experiments, as LIT-001 had no significant effects on expression of partner preference if administered following a shorter (2 hour-long) cohabitation. Instead, this difference agrees with the hypothesis that the activation of oxytocin receptors acts as a signal of presence of a social partner. Our results indicate that the effects of pharmacological activation of oxytocin receptors crucially depend on the phase of social attachments.
针对催产素系统的活性来调节社会联系引起了人们的广泛兴趣。然而，外源性给予催产素的研究面临着其稳定性低、脑渗透性差和受体特异性不足的问题。使用小分子催产素受体特异性激动剂可以克服这些问题。在临床环境中测试具有脑渗透性的催产素受体激动剂的潜在效果之前，评估这种激动剂如何影响动物模型中的社会联系非常重要。兼性一夫一妻制的草原田鼠能够在成年个体之间形成长期的社会依恋关系，是进行此类测试的理想啮齿动物模型。因此，在一系列实验中，我们研究了最近开发的催产素受体特异性激动剂LIT-001对草原田鼠配偶偏好的获得和表达的影响，配偶偏好是一种成熟的配对结合模型。如预期的那样，LIT-001（10毫克/千克，腹腔注射）在4小时同居前给药时促进了配偶偏好的获得。相比之下，在4小时同居后注射溶剂的动物表现出显著的配偶偏好，而注射LIT-（此处原文有误，推测应为LIT-001）的动物则没有表现出这种配偶偏好。这一结果表明，在配对结合表达过程中激活催产素受体可以抑制配偶偏好。LIT-001对获得与表达的影响差异并非由于实验之间配偶偏好的基础差异，因为如果在较短（2小时）同居后给药，LIT-001对配偶偏好的表达没有显著影响。相反，这种差异与催产素受体激活作为社会伴侣存在信号的假设一致。我们的结果表明，催产素受体的药理激活作用关键取决于社会依恋的阶段。
