Effects of GABA and some GABA analogues on respiratory regulation in the preterm rabbit

Preterm neonatal rabbits (gestational age 29 days) were given GABA (750 mg/kg) or the GABA-like drugs muscimol (2 mg/kg) and GHBA (375 mg/kg) intraperitoneally. Basal respiration and the ventilatory response to 10% CO2 were studied, before and after drug administration, in a whole body plethysmograph during halothane anesthesia. The three drugs tested all caused a decrease in minute volume. The decrease in minute volume was mainly due to a decrease in tidal volume after GABA and muscimol, while GHBA reduced minute volume due to a decrease in respiratory frequency. A decrease in respiratory frequency was also seen after muscimol administration. Changes in the respiratory time intervals were seen after muscimol and GHBA both causing significant increases in expiratory and respiratory time. 'Inspiratory drive' and 'respiratory timing mechanisms' were evaluated by VT/TI and TI/TTOT, respectively. GABA and muscimol reduced both VT/TI and TI/TTOT while GHBA only reduced TI/TTOT. Addition of 10% CO2 to the inhalation gas caused an increase in tidal volume and minute volume during control conditions. This response to CO2 was abolished by GABA and GHBA treatment. Our findings demonstrate that GABA and GABA-like drugs cause respiratory depression in the preterm neonate. Central mechanisms are most likely involved in this response. These findings may be relevant to the irregular or apneic breathing sometimes seen in the preterm human infant.