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

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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.