Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Neuropharmacology. 2018 May 1;133:366-374. doi: 10.1016/j.neuropharm.2018.02.007. Epub 2018 Feb 15.
Several studies on humans and mice support oxytocin's role in improving social behaviour, but its use in pharmacotherapy presents some important limiting factors. To date, it is emerging a pharmacological potential for melanocortin 4 receptor (MC4R) agonism in social deficits treatment. Recently, we demonstrated that the deletion of the NFKB1 gene, which encodes the p50 NF-κB subunit, causes impairment in social behaviours, with reductions in social interactions in mice. In this work, we tested the acute effects of THIQ, a selective melanocortin 4 receptor (MC4R) agonist. THIQ treatment increased social interactions both in wild type and p50 mice. In particular, after treatment with THIQ, p50 mice showed a prosocial behaviour analogous to that of basal WT mice. Moreover, intranasal treatment with an oxytocin antagonist blocked social interactions induced by THIQ, demonstrating that its prosocial effects are mediated by the oxytocin pathway. The data obtained reinforce using MC4R agonists to ameliorate social impairment in NDDs.
已有多项人体和小鼠研究支持催产素在改善社交行为方面的作用，但将其用于药物治疗存在一些重要的限制因素。迄今为止，促黑细胞皮质素 4 受体（MC4R）激动剂在治疗社交缺陷方面显示出了药理学潜力。最近，我们证明了编码 p50 NF-κB 亚单位的 NFKB1 基因缺失会导致小鼠的社交行为受损，社交互动减少。在这项工作中，我们测试了选择性 MC4R 激动剂 THIQ 的急性作用。THIQ 治疗增加了野生型和 p50 小鼠的社交互动。特别是，THIQ 治疗后，p50 小鼠表现出类似于基础 WT 小鼠的亲社会行为。此外，鼻内给予催产素拮抗剂可阻断 THIQ 诱导的社交互动，表明其亲社会作用是通过催产素途径介导的。所得数据支持使用 MC4R 激动剂来改善神经发育障碍中的社交障碍。
