Department of Clinical Psychology, Central Institute of Mental Health Mannheim and Medical Faculty Mannheim, University of Heidelberg Mannheim, Germany.
Front Neurosci. 2013 Apr 1;7:45. doi: 10.3389/fnins.2013.00045. eCollection 2013.
Although oxytocin (OT) has become a major target for the investigation of positive social processes, it can be assumed that it exerts its effects in concert with other neurotransmitters. One candidate for such an interaction is dopamine (DA). For both systems, genetic variants have been identified that influence the availability of the particular substance. A variant of the gene coding for the transmembrane protein CD38 (rs3796863), which is engaged in OT secretion, has been associated with OT plasma level. The common catechol-O-methyltransferase (COMT) val158met polymorphism is known to influence COMT activity and therefore the degradation of DA. The present study aimed to investigate OT × DA interactions in the context of an OT challenge study. Hence, we tested the influence of the above mentioned genetic variants and their interaction on the activation of different brain regions (amygdala, VTA, ventral striatum and fusiform gyrus) during the presentation of social stimuli. In a pharmacological cross-over design 55 participants were investigated under OT and placebo (PLA) by means of fMRI. Brain imaging results revealed no significant effects for VTA or ventral striatum. Regarding the fusiform gyrus, we could not find any effects apart from those already described in Sauer et al. (2012). Analyses of amygdala activation resulted in no gene main effect, no gene × substance interaction but a significant gene × gene × substance interaction. While under PLA the effect of CD38 on bilateral amygdala activation to social stimuli was modulated by the COMT genotype, no such epistasis effect was found under OT. Our results provide evidence for an OT × DA interaction during responses to social stimuli. We postulate that the effect of central OT secretion on amygdala response is modulated by the availability of DA. Therefore, for an understanding of the effect of social hormones on social behavior, interactions of OT with other transmitter systems have to be taken into account.
虽然催产素（OT）已成为研究积极社会过程的主要目标，但可以假定它与其他神经递质一起发挥作用。多巴胺（DA）就是这样一种相互作用的候选者。对于这两个系统，已经确定了影响特定物质可用性的遗传变异。编码跨膜蛋白 CD38（rs3796863）的基因的一个变体与 OT 血浆水平相关，该变体参与 OT 的分泌。众所周知，常见的儿茶酚-O-甲基转移酶（COMT）val158met 多态性会影响 COMT 活性，从而影响 DA 的降解。本研究旨在探讨 OT 挑战研究中 OT 和 DA 之间的相互作用。因此，我们测试了上述遗传变异及其相互作用对不同脑区（杏仁核、VTA、腹侧纹状体和梭状回）在呈现社会刺激时激活的影响。在药理学交叉设计中，通过 fMRI 对 55 名参与者在 OT 和安慰剂（PLA）下进行了测试。脑成像结果显示 VTA 或腹侧纹状体没有显著影响。关于梭状回，除了 Sauer 等人已经描述的那些结果外，我们没有发现任何影响。（2012）。对杏仁核激活的分析没有显示出基因主效应、基因-物质相互作用，但显示出基因-基因-物质相互作用。虽然在 PLA 下，CD38 对双侧杏仁核对社会刺激的激活的影响受 COMT 基因型调节，但在 OT 下没有发现这种上位效应。我们的研究结果为社会刺激反应中 OT 和 DA 相互作用提供了证据。我们假设，中枢 OT 分泌对杏仁核反应的影响受 DA 可用性的调节。因此，为了理解社会激素对社会行为的影响，必须考虑 OT 与其他递质系统的相互作用。
