Neuropharmacology

Biography

Biography: Thomas Grund

Abstract

Oxytocin (OXT) and Neuroeptide S (NPS) are known modulators of socio-emotional and neuroendocrine stress reponses. Both neuropeptides were shown to be released within the brain, and their receptors are abundantly expressed in hypothalamic and other limbic brain regions. Both OXT and NPS have been shown to exert robust anxiolytic effects, and we could localize such anxiolytic activity within the PVN (OXT, NPS), the central (OXT) and medial (NPS) amygdala. Anxiolytic effects of chronic OXT and acute NPS could also be found in rat models of pathological hyper-anxiety, such as in rats selectively bred for high anxiety-related behaviour. Moreover, both neuropeptides are involved in extinction of conditioned fear. However, whereas OXT was found to reverse social fear in social fear-conditioned mice, NPS seems to be effective during both social and cued fear extinction. Because of these similar behavioural effects we tested whether OXT mediates the anxiolytic effects of NPS. Indeed, central pretreatment with OXT receptor antagonist blocked NPS-induced anxiolysis in rats. Current studies are focussed on investigating the functional relationship between these neuropeptides in the context of social and cued fear conditioning and generalized anxiety. Despite the increasing knowledge regarding the behavioural effects of OXT and NPS, the receptor-mediated signaling cascades are largely unkown. We could identify several intraneuronal pathways within the PVN linked to OXT or NPS receptors, which include, for example, the MAP kinase pathway, which seems important for the local anxiolytic effects of OXT. Deeper knowledge into the molecular mechanisms of action are needed before neuropeptides can be considered a treatment option for diseases associated with socio-emotional dysfunctions. This research was supported by the Deutsche Forschungsstiftung, EU (FemNat-CD) and BMBF.