The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis
by
Konsman JP, Luheshi GN, Bluthe RM, Dantzer R
INSERM U394,
Neurobiologie Integrative,
Institut Francois Magendie,
Rue Camille Saint-Saens,
33077 Bordeaux Cedex, France.
jpkonsman@hotmail.com
Eur J Neurosci 2000 Dec; 12(12):4434-46

ABSTRACT

Cytokines act on the brain to induce fever and behavioural depression after infection. Although several mechanisms of cytokine-to-brain communication have been proposed, their physiological significance is unclear. We propose that behavioural depression is mediated by the vagus nerve activating limbic structures, while fever would primarily be due to humoral mechanisms affecting the preoptic area, including interleukin-6 (IL-6) action on the organum vasculosum of the laminae terminalis (OVLT) and induction of prostaglandins. This study assessed the effects of subdiaphragmatic vagotomy in rats on fever, behavioural depression, as measured by the social interaction test, and Fos expression in the brain. These responses were compared with induction of the prostaglandin-producing enzyme cyclooxygenase-2 and the transcription factor Stat3 that translocates after binding of IL-6. Vagotomy blocked behavioural depression after intraperitoneal injection of recombinant rat IL-1beta (25 microg/kg) or lipopolysaccharide (250 microg/kg; LPS) and prevented Fos expression in limbic structures and ventromedial preoptic area, but not in the OVLT. Fever was not affected by vagotomy, but associated with translocation of Stat3 in the OVLT and cyclooxygenase-2 induction around blood vessels. These results indicate that the recently proposed vagal link between the immune system and the brain activates limbic structures to induce behavioural depression after abdominal inflammation. Although the vagus might play a role in fever in response to low doses of LPS by activating the ventromedial preoptic area, it is likely to be overridden during more severe infection by action of circulating IL-6 on the OVLT or prostaglandins induced along blood vessels of the preoptic area.

rTMS
Stress
Options
Cytokines
Depression
Interferons
Interleukins
21st Century
Cytokines and psychiatry
Cytokines and depression
Inflammation and depression
Depressive effect of cytokines
Cytokines, stress and depression
Vegas nerve stimulation and cognition
Vagus nerve stimulation and depression
Cytokines and heart failure-induced anhedonia
The immune system, depression and antidepressants

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