Invited Symposium: Cytokines, Monoamines and Behavior



Materials & Methods


Discussion & Conclusion



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Sensitization Effects of TNF-alpha: Behavioral and Neurochemical Processes

Hayley, S (Institute of Neuroscience, Carleton University, Canada)
Brebner, K (Institute of Neuroscience, Carleton University, Canada)
Merali, Z (Dept of Cellular and Molecular Medicine, University of Ottawa, Canada)
Anisman, H (Institute of Neuroscience, Carleton University, Canada)

Contact Person: Shawn Hayley (shayley@ccs.carleton.ca)


Systemic levels of the pleiotropic cytokine, tumor necrosis factor-alpha (TNF-alpha), are elevated in various pathological states. However, scant data are available concerning the behavioral and central neurochemical effects associated with altered TNF-alpha concentrations, and whether any such effects depend upon the temporal pattern of cytokine administration. We found that systemic TNF-alpha (1.0-4.0 ug) reduced consumption of a palatable substance (suggesting illness), increased plasma corticosterone concentrations and altered monoamine turnover in hypothalamic and extrahypothalamic sites. These effects were augmented upon reexposure to low doses (1.0 ug) of the cytokine (sensitization), depending upon the time interval between the two administrations. While re-exposure to a behaviorally sub-effective dose of the cytokine (1.0 ug) 2-4 weeks following initial treatment provoked marked illness, no such effects were observed at a 1-7 day interval. The sickness behaviors (e.g. ptosis, social isolation and immobility) were accompanied by greatly elevated plasma corticosterone levels and variations of monoamines within the paraventricular nucleus (PVN). In contrast, upon reexposure 1 day after the first TNF-alpha exposure, corticosterone levels were reduced relative to non-reexposed mice indicating some degree of desensitization. However, at this time substantial increases of monoamine utilization were evident in the medial prefrontal cortex and the locus coeruleus. TNF-alpha exerts a wide array of immediate and proactive (sensitization) neuroendocrine and neurochemical effects that may be fundamental in understanding the behavioral consequences of such treatments.

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Presentation Number SAhayley0615
Keywords: monoamines, sensitization, cytokines, corticosterone, sickness

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Hayley, S; Brebner, K; Merali, Z; Anisman, H; (1998). Sensitization Effects of TNF-alpha: Behavioral and Neurochemical Processes. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/anisman/hayley0615/index.html
© 1998 Author(s) Hold Copyright