TY - JOUR
T1 - Sustained overexpression of neuropeptide S in the amygdala reduces anxiety-like behavior in rats
AU - Tillmann, Sandra
AU - Skibdal, Heidi E.
AU - Christiansen, Søren H.
AU - Gøtzsche, Casper R.
AU - Hassan, Moustapha
AU - Mathé, Aleksander A.
AU - Wegener, Gregers
AU - Woldbye, David P.D.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Adeno-associated virus
KW - Anxiety
KW - Depression
KW - Neuropeptide S
UR - http://www.scopus.com/inward/record.url?scp=85063542112&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2019.03.039
DO - 10.1016/j.bbr.2019.03.039
M3 - Journal article
C2 - 30914309
AN - SCOPUS:85063542112
SN - 0166-4328
VL - 367
SP - 28
EP - 34
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -