TY - JOUR
T1 - Systemic capsaicin pretreatment fails to block the decrease in food- motivated behavior induced by lipopolysaccharide and interleukin-1β
AU - Bret-Dibat, Jean Luc
AU - Creminon, Christophe
AU - Couraud, Jean Yves
AU - Kelly, Keith W.
AU - Dantzer, Robert
AU - Kent, Stephen
N1 - Funding Information:
We thank Dr. Chizzonite (Hoffmann-LaRoche) for the rhIL-1β, and M. C. Nevers and O. Dery for technical assistance with the biochemistry experiments. This research was supported by INSERM, INRA, DRET, Ministère de l'Environnement, Région Aquitaine (Pôle Médicament), and NIH Grant MH51569-02. J.L.B.D. was supported by the Ministry of Research and Education. S.K. was partially supported by a fellowship from the Fondation pour la Recherche Médicale.
PY - 1997
Y1 - 1997
N2 - The physiological and behavioral disturbances observed during an infection can be reproduced by systemic administration of proinflammatory cytokines (e.g., interleukin (IL)-1, IL-6, tumor necrosis factor-α) or lipopolysaccharide (LPS), a potent inducer of these cytokines. It is now well established that these molecules induce their effects by acting centrally, however, the mechanisms by which they reach central structures are not clear. We have earlier proposed that the humoral immune message is converted to a central neural activation by the action of cytokines on peripheral terminations of afferent neurons. Subdiaphragmatic vagotomy abolishes several effects of peripherally injected IL-1β and LPS (e.g., decreased food- motivated behavior and social exploration, central expression of cytokines). To further define the nature of the peripheral fibers implicated in this phenomenon, we used a potent sensory neurotoxin, capsaicin, to selectively destroy C-fiber afferents. Adult rats were injected IP with a total dose of 25 mg/kg capsaicin in a series of 10 injections over a 48-h period. Adult mice were injected IP with a total dose of 75 mg/kg in a series of seven injections over a 7-day period. Although capsaicin treatment altered visceral chemosensory function, corneal end pain sensitivity, vagal-mediated anorexic effects of cholecystokinin, and depleted levels of substance P in the thoracic spinal cord, it was completely ineffective in blocking the decrease in food-motivated behavior induced by IL-1β (4 μg/rat IP in rats) and LPS (250 μg/kg IP in rats and 400 μg/kg IP in mice). Thus, other afferents besides capsaicin-sensitive C-fibers appear to be involved in the transduction of cytokine effects during inflammatory and infectious events.
AB - The physiological and behavioral disturbances observed during an infection can be reproduced by systemic administration of proinflammatory cytokines (e.g., interleukin (IL)-1, IL-6, tumor necrosis factor-α) or lipopolysaccharide (LPS), a potent inducer of these cytokines. It is now well established that these molecules induce their effects by acting centrally, however, the mechanisms by which they reach central structures are not clear. We have earlier proposed that the humoral immune message is converted to a central neural activation by the action of cytokines on peripheral terminations of afferent neurons. Subdiaphragmatic vagotomy abolishes several effects of peripherally injected IL-1β and LPS (e.g., decreased food- motivated behavior and social exploration, central expression of cytokines). To further define the nature of the peripheral fibers implicated in this phenomenon, we used a potent sensory neurotoxin, capsaicin, to selectively destroy C-fiber afferents. Adult rats were injected IP with a total dose of 25 mg/kg capsaicin in a series of 10 injections over a 48-h period. Adult mice were injected IP with a total dose of 75 mg/kg in a series of seven injections over a 7-day period. Although capsaicin treatment altered visceral chemosensory function, corneal end pain sensitivity, vagal-mediated anorexic effects of cholecystokinin, and depleted levels of substance P in the thoracic spinal cord, it was completely ineffective in blocking the decrease in food-motivated behavior induced by IL-1β (4 μg/rat IP in rats) and LPS (250 μg/kg IP in rats and 400 μg/kg IP in mice). Thus, other afferents besides capsaicin-sensitive C-fibers appear to be involved in the transduction of cytokine effects during inflammatory and infectious events.
KW - Cytokines
KW - Feeding
KW - Spinal cord
KW - Substance P
KW - Vagus nerve
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U2 - 10.1016/S0361-9230(96)00370-X
DO - 10.1016/S0361-9230(96)00370-X
M3 - Article
C2 - 9128919
AN - SCOPUS:0030912764
SN - 0361-9230
VL - 42
SP - 443
EP - 449
JO - Brain Research Bulletin
JF - Brain Research Bulletin
IS - 6
ER -