Skip to main content

Caffeine Reversal of Opioid-Evoked and Endogenous Inspiratory Depression in Perinatal Rat En Bloc Medullas and Slices

  • Conference paper
  • First Online:
New Frontiers in Respiratory Control

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 669))

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ballanyi, K. (2004) Neuromodulation of the perinatal respiratory network. Curr. Neuropharmacol. 2, 221–243.

    Article  CAS  Google Scholar 

  • Ballanyi, K., Lalley, P.M., Hoch, B., and Richter, D.W. (1997) cAMP-dependent reversal of opioid- and prostaglandin-mediated depression of the isolated respiratory network in newborn rats. J. Physiol. 504, 127–134.

    Article  CAS  PubMed  Google Scholar 

  • Ballanyi, K., Onimaru, H., and Homma, I. (1999) Respiratory network function in the isolated brainstem-spinal cord of newborn rats. Prog. Neurobiol. 59, 583–634.

    Article  CAS  PubMed  Google Scholar 

  • Ballanyi, K. and Ruangkittisakul, A. (2009) Structure-function analysis of rhythmogenic inspiratory pre-Bötzinger complex networks in “calibrated” newborn rat brainstem slices. Respir. Physiol. Neurobiol. 168, 158–178.

    Article  PubMed  Google Scholar 

  • Fredholm, B.B., Bättig, K., Holmén, J., Nehlig, A., and Zvartau, E.E. (1999) Actions of caffeine in the brain with special reference to factors that contribute to its wide-spread use. Pharmacol. Rev. 51, 83–133.

    CAS  PubMed  Google Scholar 

  • Herlenius, E., Adén, U., Tang, L.Q., and Lagercrantz, H. (2002) Perinatal respiratory control and its modulation by adenosine and caffeine in the rat. Pediatr. Res. 51, 4–12.

    Article  CAS  PubMed  Google Scholar 

  • Manzke, T., Guenther, U., Ponimaskin, E.G., Haller, M., Dutschmann, M., Schwarzacher, S., and Richter, D.W. (2003) 5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science 301, 226–229.

    Article  CAS  PubMed  Google Scholar 

  • Montandon, G., Kinkead, R., and Bairam, A. (2007) Disruption of adenosinergic modulation of ventilation at rest and during hypercapnia by neonatal caffeine in young rats: Role of adenosine A(1) and A(2A) receptors. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1621–R1631.

    CAS  PubMed  Google Scholar 

  • Panaitescu, B., Ruangkittisakul, A., and Ballanyi, K. (2009) Silencing by raised extracellular Ca2+ of pre-Bötzinger complex neurons in newborn rat brainstem slices without change of membrane potential or input resistance. Neurosci. Lett. 456, 25–29.

    Article  CAS  PubMed  Google Scholar 

  • Peña, F. and García, O. (2006) Breathing generation and potential pharmacotherapeutic approaches to central respiratory disorders. Curr. Med. Chem. 13, 2681–2693.

    Article  PubMed  Google Scholar 

  • Richter, D.W., Lalley, P.M., Pierrefiche, O., Haji, A., Bischoff, A.M., Wilken, B., and Hanefeld, V. (1997) Intracellular signal pathways controlling respiratory neurons. Resp. Physiol. 110, 113–123.

    Article  CAS  Google Scholar 

  • Ruangkittisakul, A., Secchia, L., Bornes, T.D., Palathinkal, D.M., and Ballanyi, K. (2007) Dependence on extracellular Ca2+/K+ antagonism of inspiratory centre rhythms in slices and en bloc preparations of newborn rat brainstem. J. Physiol. 584, 489–508.

    Article  CAS  PubMed  Google Scholar 

  • Ruangkittisakul, A. and Ballanyi, K. (2006) Reversal by phosphodiesterase-4 blockers of in vitro apnea in the isolated brainstem-spinal cord preparation from newborn rats. Neurosci. Lett. 401, 194–198.

    Article  CAS  PubMed  Google Scholar 

  • Ruangkittisakul, A., Schwarzacher, S.W., Secchia, L., Poon, B.Y., Ma, Y., Funk, G.D., and Ballanyi, K. (2006) High sensitivity to neuromodulator-activated signalling pathways at physiological [K+] of confocally-imaged respiratory centre neurons in online-calibrated newborn rat brainstem slices. J. Neurosci. 26, 11870–11880.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

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).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Klaus Ballanyi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this paper

Cite this paper

Ruangkittisakul, A., Panaitescu, B., Kuribayashi, J., Ballanyi, K. (2010). Caffeine Reversal of Opioid-Evoked and Endogenous Inspiratory Depression in Perinatal Rat En Bloc Medullas and Slices. In: Homma, I., Onimaru, H., Fukuchi, Y. (eds) New Frontiers in Respiratory Control. Advances in Experimental Medicine and Biology, vol 669. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5692-7_25

Download citation

Publish with us

Policies and ethics