Adenosine a1 receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release

George C. Gettys, Fang Liu, Ed Kimlin, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Clinical and preclinical data demonstrate the analgesic actions of adenosine. Central administration of adenosine agonists, however, suppresses arousal and breathing by poorly understood mechanisms. This study tested the two-tailed hypothesis that adenosine A1 receptors in the pontine reticular formation (PRF) of C57BL/6J mice modulate breathing, behavioral arousal, and PRF acetylcholine release. Methods: Three sets of experiments used 51 mice. First, breathing was measured by plethysmography after PRF microinjection of the adenosine A1 receptor agonist N-sulfophenyl adenosine (SPA) or saline. Second, mice were anesthetized with isoflurane and the time to recovery of righting response (RoRR) was quantified after a PRF microinjection of SPA or saline. Third, acetylcholine release in the PRF was measured before and during microdialysis delivery of SPA, the adenosine A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine, or SPA and 1, 3-dipropyl-8- cyclopentylxanthine. Results: First, SPA significantly decreased respiratory rate (-18%), tidal volume (-12%), and minute ventilation (-16%). Second, SPA concentration accounted for 76% of the variance in RoRR. Third, SPA concentration accounted for a significant amount of the variance in acetylcholine release (52%), RoRR (98%), and breathing rate (86%). 1, 3-dipropyl-8-cyclopentylxanthine alone caused a concentration-dependent increase in acetylcholine, a decrease in RoRR, and a decrease in breathing rate. Coadministration of SPA and 1, 3-dipropyl-8-cyclopentylxanthine blocked the SPA-induced decrease in acetylcholine and increase in RoRR. Conclusions: Endogenous adenosine acting at adenosine A1 receptors in the PRF modulates breathing, behavioral arousal, and acetylcholine release. The results support the interpretation that an adenosinergic-cholinergic interaction within the PRF comprises one neurochemical mechanism underlying the wakefulness stimulus for breathing.

Original languageEnglish (US)
Pages (from-to)327-336
Number of pages10
JournalAnesthesiology
Volume118
Issue number2
DOIs
StatePublished - Feb 1 2013

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Adenosine A1 Receptors
Adenosine
Acetylcholine
Respiration
Anesthesia
Righting Reflex
Arousal
Microinjections
Pontine Tegmentum
Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Plethysmography
Wakefulness
Isoflurane
Tidal Volume
Microdialysis
Respiratory Rate
Inbred C57BL Mouse
Cholinergic Agents
Ventilation

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

Cite this

Adenosine a1 receptors in mouse pontine reticular formation depress breathing, increase anesthesia recovery time, and decrease acetylcholine release. / Gettys, George C.; Liu, Fang; Kimlin, Ed; Baghdoyan, Helen; Lydic, Ralph.

In: Anesthesiology, Vol. 118, No. 2, 01.02.2013, p. 327-336.

Research output: Contribution to journalArticle

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AU - Gettys, George C.

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AU - Lydic, Ralph

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