Neurobehavioral alterations in mice with a targeted deletion of the tumor necrosis factor-α gene: Implications for emotional behavior

Tumor necrosis factor-α (TNF-α) 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-α in cognitive and emotional function using mice with targeted deletions of the TNF-α gene. TNF-α-(-/-) 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-α-(-/-) mice revealed a significant increase in serotonin metabolism in the brain. These findings suggest a role for endogenous TNF-α in emotional behavior, which may possibly be related to alterations of serotonine metabolism. Copyright (C) 2000 .