HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/R922    most recent 00059.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Montandon, G. Articles by Kinkead, R. Search for Related Content PubMed PubMed Citation Articles by Montandon, G. Articles by Kinkead, R.

EXERCISE AND RESPIRATORY PHYSIOLOGY

Neonatal caffeine induces sex-specific developmental plasticity of the hypoxic respiratory chemoreflex in adult rats

¹Department of Physiology, University of Toronto, Ontario; and ²Department of Pediatrics, Laval University, Centre de Recherche Hôpital St-François d'Assise, Québec, Canada

Submitted 27 January 2008 ; accepted in final form 26 June 2008

Caffeine is widely used to treat apneas of prematurity during the neonatal period; however, the potential consequences of administering a neonatal caffeine treatment (NCT) during a critical period for respiratory control development are unknown. The present study therefore determined whether NCT in rats alters the hypoxic respiratory chemoreflex measured at adulthood. Newborn rats received either caffeine (15 mg/kg) or water (control) each day from postnatal day 3 to 12. The ventilatory response to a hypoxic challenge (inspired O₂ fraction = 0.12) was first evaluated in awake adult female and male rats using whole body plethysmography. Results showed that NCT increased the initial phase of the breathing frequency response to hypoxia in males only. This result was confirmed in anesthetized and artificially ventilated adult male rats where NCT also increased the phrenic burst frequency response to hypoxia. RT-PCR assessment of mRNA encoding for adenosine A_1A and A_2A receptors, dopamine D₂ receptors, and tyrosine hydroxylase in the rat carotid bodies showed that NCT enhanced mRNA expression levels of adenosine A_2A, dopamine D₂ receptors, and tyrosine hydroxylase of males but not females. Subsequent experiments on awake male rats showed that injection of the adenosine A_2A receptor antagonist ZM2413855 (1 mg/kg ip) before ventilatory measurements abolished, in NCT rats, the enhanced respiratory frequency response observed during the early phase of hypoxia. We propose that NCT elicits a sex-specific increase in the hypoxic respiratory chemoreflex, which is related, at least partially, to an enhancement in adenosine A_2A receptors in the rat carotid body.

caffeine; control of breathing; development; sexual dimorphism

This article has been cited by other articles:

				G. Montandon, R. L. Horner, R. Kinkead, and A. Bairam Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats J. Physiol., November 15, 2009; 587(22): 5493 - 5507. [Abstract] [Full Text] [PDF]

				D. Lumbroso and V. Joseph Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R421 - R427. [Abstract] [Full Text] [PDF]