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 modulat or of the function of the central nervous system. In the present study, we investigated a role of endogenous TNF-alpha in cognitive and emotional func tion using mice with targeted deletions of the TNF-alpha gene. TNF-alpha-(- /-) mice showed normal diurnal rhythms of spontaneous locomotor activity an d cognitive functions. Emotional behavior in the mutant mice, however, was significantly altered, which manifested in the performance in the open-fiel d, elevated plus maze, and forced swimming tests. The altered performance i n the elevated plus maze test was significantly alleviated by treatment wit h diazepam. Postmortem brain analysis of TNF-alpha-(-/-) mice revealed a si gnificant increase in serotonin metabolism in the brain. These findings sug gest a role for endogenous TNF-alpha in emotional behavior, which may possi bly be related to alterations of serotonine metabolism. (C) 2000 Published by Elsevier Science B.V.