Bicuculline Enhances Basal Ventilation in 12 Day‐Old Rats Chronically Treated with Caffeine.

Abstract

Caffeine is the 1st line pharmacological treatment for apnea of prematurity and can be administered for days to weeks. Because of the close interaction between adenosine and GABA on respiratory control in newborn subjects, we tested here the hypothesis that chronic inhibition of adenosine receptors by daily caffeine administration modulates GABAa receptors function. In 12-day-old rats that were daily gavaged with water (control) or caffeine (15mg/kg) from postnatal day 3-12, we measured respiratory frequency, tidal volume, minute ventilation and metabolism (oxygen consumption and CO2 production) in normoxia while rats were awake and un-anesthetized (plethysmography). These measurements were performed following a single i.p. injection of vehicle (DMSO) or bicuculline (2mg/kg, specific GABAa receptor antagonist). In control rats, basal ventilation was not different between vehicle and bicuculline. In caffeine rats, bicuculline increased basal ventilation (+50%) compared to vehicle. No changes in metabolism were observed in control or caffeine rats. These results show that chronic caffeine administration induces important changes in GABAa receptor response that may be related to an increase in receptor density and/or in their sensitivity to GABA. Funded by CIHR (MOP 119272).