Inga Neumann

University of Regensburg, Germany

Abstract

[O20] Regulation of behavioural, neuroendocrine and neuronal stress responses by brain neuropeptides: oxytocin (OXT), prolactin (PRL) and neuropeptide S (NPS)

Brain neuropeptides represent viable novel research candidates for the development of effective treatment strategies of affective and stress-related disorders. The neuropeptides OXT, PRL and NPS are significantly involved in the regulation of complex stress responses including the activity of the hypothalamo-pituitary-adrenal (HPA) axis and anxiety-related behaviours. OXT and PRL were shown to be released within limbic brain regions, e.g. the hypothalamic paraventricular nucleus (PVN) and the amygdala, in response to diverse social and stressful stimuli. OXT, PRL and NPS receptors are widely distributed in brain regions relevant for stress regulation. Moreover, OXT, PRL and NPS exert anxiolytic actions which could be localized, for example, within the PVN, as well as within the central and medial amygdala, respectively. The acute behavioural effects of OXT within the PVN were found to be mediated via the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade, as local blockade of this signaling pathway prevented the OXT-induced anxiolysis2. Also, icv PRL activates the ERK1/2 cascade within the hypothalamus, and PRL-induced phospho-ERK localization was found in CRH neurons of the PVN. Thus, the inhibitory effects of PRL on behavioural and HPA axis stress responses are likely to be mediated via this pathway and alteration of CRH neuronal activity. The prominent stimulatory action of OXT and PRL on the ERK pathway in the hypothalamus may also mediate neuroplasticity of the neuroendocrine system during lactation. In the peripartum period, both neuropeptide systems are highly activated and fulfill not only various reproductive functions, but also play an important role in physiological and behavioural adaptations of the stress response.  Indeed, chronic PRL treatment mimicking high brain PRL activity attenuates the behavioural, hormonal and neuronal stress response and reverses the chronic stress-induced impairment of hippocampal neurogenesis.

Importantly, anxiolytic effects of chronic OXT and acute NPS were also found in a psychopathological rat model, i.e. in rats selectively bred for high (HAB) anxiety-related behaviour. Thus, these neuropeptides may represent potential targets for the development of therapeutic strategies to treat anxiety- and stress-related diseases.

This research was supported by the Deutsche Forschungsstiftung and BMBF