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Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
08:49

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention

Published on: October 16, 2013

Adenosine A(1) receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time,

George C Gettys1, Fang Liu, Ed Kimlin

  • 1Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109-5615, USA.

Anesthesiology
|December 25, 2012
PubMed
Abstract

Insights

Adenosine A1 receptors in the pontine reticular formation (PRF) regulate breathing and arousal. This adenosinergic-cholinergic interaction in the PRF is key to the wakefulness stimulus for breathing.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Respiratory Physiology

Background:

  • Adenosine is known for its analgesic effects.
  • Central adenosine agonists suppress arousal and breathing via unclear mechanisms.
  • Adenosine A1 receptors in the pontine reticular formation (PRF) were investigated for their role in modulating breathing, arousal, and acetylcholine release.

Purpose of the Study:

  • To test the hypothesis that adenosine A1 receptors in the PRF modulate breathing, behavioral arousal, and acetylcholine release.
  • To elucidate the neurochemical mechanisms underlying the wakefulness stimulus for breathing.

Main Methods:

  • Experiments involved microinjections into the PRF of C57BL/6J mice.
  • Breathing was measured using plethysmography.
  • Recovery of righting response (RoRR) and acetylcholine release were quantified following agonist/antagonist administration.

Main Results:

  • Adenosine A1 receptor agonist (SPA) decreased respiratory rate, tidal volume, and minute ventilation.
  • SPA concentration significantly influenced RoRR, acetylcholine release, and breathing rate.
  • Antagonist (1,3-dipropyl-8-cyclopentylxanthine) increased acetylcholine and decreased RoRR and breathing rate, effects blocked by SPA coadministration.

Conclusions:

  • Endogenous adenosine acting on PRF A1 receptors modulates breathing, arousal, and acetylcholine release.
  • An adenosinergic-cholinergic interaction within the PRF is a neurochemical mechanism for the wakefulness stimulus for breathing.

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