EXPLORATORY AND DISPLACEMENT BEHAVIOR IN TRANSGENIC MICE EXPRESSING HIGH-LEVELS OF BRAIN TNF-ALPHA

Studies reported recently have shown that tumor necrosis factor-alpha (TNF-alpha) a cytokine released by macrophages and monocytes plays a k ey role in inflammatory processes and immune and neuro-endocrine regul ation. TNF-alpha is also produced in the central nervous system (CNS). However, the role of this cytokine in the CNS is largely unknown, alt hough evidence indicates that it is involved in various neurobehaviora l manifestations. Using transgenic mice expressing high amounts of mur ine TNF-alpha transgene in the neurons of the CNS, we investigated the stereotyped, exploratory, and displacement activities in the hole-boa rd and black/white box. Transgenic mice and their normal control litte rmates were hybrids of the CBA x C57BL/6 genetic backgrounds and were obtained by backcrossing the CBA x C57BL/6 founder female and her prog eny with Fl hybrid mates. Transgenic mice did not show changes in the stereotyped behavior on the hole-board, but they displayed several alt erations in the exploratory activities both in the hole-board and blac k/white box. Transgenic mice also exhibited an increase in grooming wh en exposed to a highly unfamiliar environmental stimuli in the black/w hite box. The study suggests that supranormal endogenous TNF-alpha in the brain affects the behavioral responses to stressful conditions. (C ) 1998 Elsevier Science Inc.