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Neurobehavioural activation during peripheral immunosuppression.

Gustavo Pacheco-López1, Raphael Doenlen, Ute Krügel

  • 1Swiss Federal Institute of Technology Zurich, Physiology and Behaviour Laboratory, Zurich, Switzerland. gustavo-pacheco@ethz.ch

The International Journal of Neuropsychopharmacology
|January 6, 2012
PubMed
Summary
This summary is machine-generated.

Cyclosporine A (CsA) triggers learned immune suppression by directly acting on the brain, not through the vagus nerve. This discovery reveals a novel pathway for drug-induced immunosuppression detection.

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Area of Science:

  • Neuroscience
  • Immunology
  • Behavioral Conditioning

Background:

  • Immune functions can be behaviorally conditioned, similar to other physiological responses.
  • Learned immunosuppression is induced by pairing a taste with cyclosporine A (CsA), mediated by the insular cortex and amygdala.

Purpose of the Study:

  • To investigate the afferent pathways through which the brain detects CsA.
  • To determine if CsA is sensed by the vagus nerve or acts directly on the brain.

Main Methods:

  • Peripheral administration of CsA in an associative learning paradigm.
  • Measurement of neuronal activity (electric activity, c-Fos expression, noradrenaline release) in the insular cortex and amygdala.
  • Vagal deafferentation to assess the role of the vagus nerve.

Main Results:

  • Peripheral CsA administration increased neuronal activity in the insular cortex and amygdala.
  • This increased activity was unaffected by vagal deafferentation.
  • Results suggest partial direct action of CsA on cortico-amygdaloid structures and brainstem regions (area postrema, nucleus of the solitary tract).

Conclusions:

  • CsA appears to directly act on the brain to induce conditioned immunosuppression.
  • The vagus nerve is not the primary afferent pathway for CsA detection in this context.
  • A novel, yet unknown, transduction mechanism may be involved in CsA's direct action on the brain.