Sustained overexpression of neuropeptide S in the amygdala reduces anxiety-like behavior in rats

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  • Sandra Tillmann
  • ,
  • Heidi E. Skibdal, København Universitet
  • ,
  • Søren H. Christiansen, University of Copenhagen
  • ,
  • Casper R. Gøtzsche, University of Copenhagen
  • ,
  • Moustapha Hassan, Karolinska Institutet
  • ,
  • Aleksander A. Mathé, Karolinska Institutet
  • ,
  • Gregers Wegener
  • David P.D. Woldbye, University of Copenhagen

Neuropeptide 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.

Original languageEnglish
JournalBehavioural Brain Research
Pages (from-to)28-34
Number of pages7
Publication statusPublished - Jul 2019

    Research areas

  • Adeno-associated virus, Anxiety, Depression, Neuropeptide S

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