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Lack of neuropeptide FF signalling in mice leads to reduced repetitive behavior, altered drinking behavior, and fuel type selection


Although best known for their involvement in modulating nociception, Neuropeptide FF (NPFF) group peptides have been suggested to fulfil a variety of biological functions such as feeding, anxiety behaviors and thermogenesis. However, evidence supporting these functions of NPFF is mostly pharmacological, leaving the physiological relevance unaddressed. Here we examined the physiological impact of lack of NPFF signalling in both genders using a Npff(-/-) mouse model. NPFF expression in the mouse is restricted to the spinal cord and brainstem while its cognate receptor NPFFR2 has wider distribution throughout the brain. Both male and female Npff(-/-) mice showed reduced repetitive behaviors evidenced in the marble burying test and self-grooming test. A decrease in anxiety-related behaviors in the Npff(-/-) mice was also observe in the open field test and to a lesser degree in an elevated plus maze test. Moreover, both male and female Npff(-/-) mice exhibited increased water intake resulting from increases in drinking size, rather than number of drinking events. During a fasting-refeeding challenge, Npff(-/-) mice of both genders displayed alterations in reparatory exchange ratio that reflect a greater fuel type flexibility. Npff(-/-) mice were otherwise wild-type-like regarding body weight, body composition, feeding behaviors, locomotion or energy expenditure. Together, these findings reveal the important physiological roles of NPFF signalling in the regulation of anxiety-related and repetitive behaviors, fluid homeostasis and oxidative fuel selection, highlighting the therapeutical potential of the NPFF system in a number of behavioral and metabolic disorders.

Type Journal
ISBN 1530-6860 (Electronic) 0892-6638 (Linking)
Authors Zhang, L.; Koller, J.; Ip, C. K.; Gopalasingam, G.; Bajaj, N.; Lee, N. J.; Enriquez, R. F.; Herzog, H.
Responsible Garvan Author Prof Herbert Herzog
Publisher Name FASEB JOURNAL
Published Date 2021-11-30
Published Volume 35
Published Issue 11
Published Pages e21980
Status Published in-print
DOI 10.1096/fj.202100703R
URL link to publisher's version