Y1 receptors regulate aggressive behavior by modulating serotonin pathways.
Neuropeptide Y (NPY) is pivotal in the coordinated regulation of food intake, growth, and reproduction, ensuring that procreation and growth occur only when food is abundant and allowing for energy conservation when food is scant. Although emotional and behavioral responses from the higher brain are known to be involved in all of these functions, understanding of the coordinated regulation of emotion/behavior and physiological functions is lacking. Here, we show that the NPY system plays a central role in this process because ablation of the Y1 receptor gene leads to a strong increase in territorial aggressive behavior. After exposure to the resident-intruder test, expression of c-fos mRNA in Y1-knockout mice is significantly increased in the medial amygdala, consistent with the activation of centers known to be important in regulating aggressive behavior. Expression of the serotonin [5-hydroxytryptamine (5-HT)] synthesis enzyme tryptophan hydroxylase is significantly reduced in Y1-deficient mice. Importantly, treatment with a 5-HT-1A agonist, (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide, abolished the aggressive behavior in Y1-knockout mice. These results suggest that NPY acting through Y1 receptors regulates the 5-HT system, thereby coordinately linking physiological survival mechanisms such as food intake with enabling territorial aggressive behavior.
Neurobiology Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010, Australia.
Tim
T
Karl
Shu
S
Lin
Christoph
C
Schwarzer
Amanda
A
Sainsbury
Michelle
M
Couzens
Walter
W
Wittmann
Dana
D
Boey
Stephan
S
von Hörsten
Herbert
H
Herzog
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000374:Aggression / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009478:Neuropeptide Y / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D017476:Receptors, Neuropeptide Y; D017366:Serotonin Receptor Agonists; C097212:neuropeptide Y-Y1 receptor; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D014365:Tryptophan Hydroxylase