• Sandra Tillmann, Heidi E Skibdal, Søren H Christiansen, Casper R Gøtzsche, Moustapha Hassan, Aleksander A Mathé, Gregers Wegener, and Woldbye David P D DPD Laboratory of Neural Plasticity, Institute of Neuroscience, University of Copenhagen, Copenhagen, Denmark..
• Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
• Behav. Brain Res. 2019 Jul 23; 367: 28-34.

AbstractNeuropeptide S (NPS) has shown anxiolytic-like effects in rodents after acute administration, but its long-term effects remain unknown. Gene therapy enables the targeted delivery of DNA to cell nuclei, and recombinant adeno-associated viral (rAAV) vectors have been identified as suitable tools for stable overexpression. Thus, to explore the effects of long-term expression of NPS, the present study examined anxiety- and depressive-like effects after rAAV-mediated NPS overexpression in the rat amygdala. Compared to rats injected with an empty control vector (rAAV-Empty), rAAV-NPS treatment was associated with reduced anxiety-like behavior in the elevated plus maze and light-dark box, but did not affect depressive-like behavior in the forced swim test. Importantly, rAAV-NPS did not cause confounding effects on locomotion or bodyweight as opposed to currently used anxiolytic drugs. Immunohistochemical stainings revealed NPS-positive cells in the central and basolateral region of the amygdala in rAAV-NPS but not rAAV-Empty rats, indicating successful transduction. Our study provides novel evidence for sustained anxiolytic-like properties of NPS by transgenic overexpression. These data suggest that rAAV-NPS application deserves further attention as a potential treatment strategy for anxiety in humans.Copyright © 2019 Elsevier B.V. All rights reserved.

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