Oxytocin activity in the hypothalamus: from intracellular signalling to anxiety-like behaviour

与自杀有关的障碍是最常见的精神病理学。神经肽催产素（OXT）通过下丘脑室旁核（PVN）减少焦虑和应激反应。然而，详细的抗焦虑活性的分子和生化机制是未知的，但需要更好的理解，以确定新的药理学治疗目标。基于我们的观察，中枢OXT的抗焦虑作用涉及活化的丝裂原活化蛋白激酶（MAPK）途径，导致细胞外信号调节激酶（ERK）磷酸化下丘脑神经元，我们的目标是确定其他OXT激活的途径在体外和体内，以及它们的细胞内相互作用调节大鼠的焦虑相关行为。此外，根据我们的初步数据OXT诱导的下丘脑基因表达的变化（微阵列研究），我们进一步希望确定急性或长期OXT诱导的抗焦虑作用的重要性，并确定其控制的细胞内级联。分子、生化和行为分析的整合将揭示参与脑OXT抗焦虑活性的重要神经因子，并可能提供可能的治疗靶点。

Anxiety-related disorders are the most common psychopathologies. The neuropeptide oxytocin (OXT) reduces anxiety and stress responses specifically via the hypothalamic paraventricular nucleus (PVN). However, detailed molecular and biochemical mechanisms underlying the anxiolytic activity are unknown, but a better understanding is desired in order to identify novel pharmacological targets for treatment. Based on our observations that the anxiolytic action of central OXT involves the activation of the mitogen-activated protein kinase (MAPK) pathway leading to extracellular signal-regulated kinase (ERK) phosphorylation in hypothalamic neurons, we aim to identify other OXT-activated pathways in vitro and in vivo as well as their intracellular interactions regulating anxiety-related behaviour in rats. Moreover, based on our preliminary data of OXT-induced alterations in hypothalamic gene expression (microarray studies), we further want to identify the importance of selected target genes for acute or prolonged OXT-induced anxiolysis and determine their control by the intracellular cascades. The integration of molecular, biochemical, and behavioural analyses will reveal important neuronal factors that are involved in the anxiolytic activity of brain OXT, and may provide possible therapeutic targets.