Caffeine Reversal of Opioid-Evoked and Endogenous Inspiratory Depression in Perinatal Rat En Bloc Medullas and Slices
Caffeine counters endogenous or drug-evoked depression of breathing in (preterm) infants. Despite its common clinical use, little is known on central nervous mechanisms of its stimulatory respiratory action. We show that millimolar concentrations of caffeine are needed in perinatal rat en bloc medullas and medullary slices for stimulation of fictive inspiratory rhythms that were either endogenously slow in fetuses or depressed by prostagandins or opioids. Findings suggests that caffeine blocks phospodiesterase-4 thus raising cAMP in rhythmogenic pre-Bötzinger complex (preBötC) networks and/or cells driving the inspiratory preBötC.
KeywordsEndogenous Depression Agonist DAMGO Medullary Slice Endogenous Neuromodulator Medullary Respiratory Neuron
Supported by CIHR, AHFMR, CFI and ISRIP/ASRA. KB is a AHFMR Scientist. BP and AR have been awarded a CIHR studentship (MFN training grant).
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