title: Identification of a role for the ventral hippocampus in neuropeptide S-elicited anxiolysis.
abstract: Neuropeptide S (NPS) increasingly emerges as a potential novel treatment option for anxiety diseases like panic and posttraumatic stress disorder. However, the neural underpinnings of its anxiolytic action are still not clearly understood. Recently, we reported that neurons of the ventral hippocampus (VH) take up intranasally administered fluorophore-conjugated NPS and, moreover, that application of NPS to mouse brain slices affects neurotransmission and plasticity at hippocampal CA3-CA1 synapses. Although these previous findings define the VH as a novel NPS target structure, they leave open whether this brain region is directly involved in NPS-mediated anxiolysis and how NPS impacts on neuronal activity propagation in the VH. Here, we fill this knowledge gap by demonstrating, first, that microinjections of NPS into the ventral CA1 region are sufficient to reduce anxiety-like behavior of C57BL/6N mice and, second, that NPS, via the NPS receptor, rapidly weakens evoked neuronal activity flow from the dentate gyrus to area CA1 in vitro. Additionally, we show that intranasally applied NPS alters neurotransmission and plasticity at CA3-CA1 synapses in the same way as NPS administered to hippocampal slices. Thus, our study provides, for the first time, strong experimental evidence for a direct involvement of the VH in NPS-induced anxiolysis and furthermore presents a novel mechanism of NPS action.
authors.affiliation: RG Neuronal Network Dynamics, Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Julien
authors.initials: J
authors.lastname: Dine
authors.forename: Irina A
authors.initials: IA
authors.lastname: Ionescu
authors.forename: Jens
authors.initials: J
authors.lastname: Stepan
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Yen
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Rainer
authors.initials: R
authors.lastname: Landgraf
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D009479:Neuropeptides
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