Neurobehavioral alterations in mice with a targeted deletion of the tumor necrosis factor-alpha gene: implications for emotional behavior.
Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important modulator of the function of the central nervous system. In the present study, we investigated a role of endogenous TNF-alpha in cognitive and emotional function using mice with targeted deletions of the TNF-alpha gene. TNF-alpha-(-/-) mice showed normal diurnal rhythms of spontaneous locomotor activity and cognitive functions. Emotional behavior in the mutant mice, however, was significantly altered, which manifested in the performance in the open-field, elevated plus maze, and forced swimming tests. The altered performance in the elevated plus maze test was significantly alleviated by treatment with diazepam. Postmortem brain analysis of TNF-alpha-(-/-) mice revealed a significant increase in serotonin metabolism in the brain. These findings suggest a role for endogenous TNF-alpha in emotional behavior, which may possibly be related to alterations of serotonine metabolism.
Yamada
K
K
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, 466-8560, Nagoya, Japan.
Iida
R
R
Miyamoto
Y
Y
Saito
K
K
Sekikawa
K
K
Seishima
M
M
Nabeshima
T
T
D000818:Animals; D001007:Anxiety / Q000276:immunology / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry / Q000276:immunology; D003071:Cognition / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D004644:Emotions / Q000502:physiology*; D017353:Gene Deletion; D008124:Locomotion / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D003345:Corticosterone