Invited Symposium: Cytokines, Monoamines and Behavior



Materials & Methods


Discussion & Conclusion



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Sensitization Effects of TNF-alpha: Behavioral and Neurochemical Processes

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

Materials and Methods

A dose response curve was determined for the effects of TNF-a on plasma corticosterone and levels of central monoamines norepinephrine (NE), dopamine (DA) and serotonin (5-HT) and their metabolites. Male CD-1 mice were injected i.p. with either 1.0, 2.0 or 4.0 ug of recombinant human TNF-a or sterile physiological saline. One hour later mice were decapitated and trunk blood was collected and brains were rapidly frozen. Trunk blood was analyzed for plasma corticosterone by a radioimmunoassay (RIA) which yielded less than 10% inter- and intra- assay variability. Brains were sectioned and discrete nuclei punched, including the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus, central amygdala, dorsal hippocampus and medial prefrontal cortex (PFC). Tissue punches were analyzed by HPLC for NE, DA, 5-HT and their respective metabolites MHPG, DOPAC and 5-HIAA . In a separate study chocolate milk consumption was determined after exposure to TNF-a.

In order to investigate the potential sensitizing actions of TNF-a, in a second experiment mice initially received TNF-a (4.0 ug) followed 1, 7, 14 or 28 days later by a second TNF-a treatment (1.0 ug). Three additional groups received 2 saline treatments, saline administration followed 2 weeks later by TNF-a(1.0 ug), or TNF-a (4.0 ug) followed 2 weeks later by saline. Mice were then decapitated, and trunk blood and brain sections analyzed as described earlier. As well, using a 4-point rating scale, locomotion, social interaction and general appearance were scored to give an impression of any "sickness" the cytokine treatments may have induced. In a separate study, consumption of a palatable chocolate milk solution was calculated in mice re-exposed to TNF-a after 14 days, which again provided an index of illness (anorexia and/or anhedonia).

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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