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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

GABA-mediated neurotransmission in the nucleus of the solitary tract alters resting ventilation following exposure to chronic hypoxia in conscious rats

Centre for the Neurobiology of Stress, Department of Life Sciences, University of Toronto at Scarborough, Toronto, Ontario, Canada

Submitted 2 September 2005 ; accepted in final form 8 June 2006

This study investigated whether changes in GABA-mediated neurotransmission within the nucleus of the solitary tract (NTS) contribute to the changes in breathing (resting ventilation and the acute HVR) that occur following exposure to chronic hypoxia (CH). Rats were exposed to 9 days of hypobaric hypoxia (0.5 atm) and then subjected to acute hypoxic breathing trials before and after bilateral microinjections of GABA, bicuculline (a GABA_A-receptor antagonist), or bicuculline plus CGP-35348 (a GABA_B receptor antagonist) into the caudal regions of the NTS. Breathing was measured using whole body plethysmography. CH caused an increase in resting ventilation when the animals were breathing 30% O₂ but did not alter ventilation during acute hypoxia (10% O₂). GABA alone had no effect on breathing in either the control or chronically hypoxic rats. Bicuculline and bicuculline/CGP had no effect on breathing in control rats. Following CH, bicuculline and bicuculline/CGP reduced minute ventilation (VI) during acute exposure to 30% O₂ but had no effect during acute exposure to 10% O₂. The bicuculline-induced reduction in VI resulted from a decrease in breathing frequency (fR) and tidal volume (VT). The bicuculline/CGP-induced reduction in VI was due to a decrease in fR with no change in VT. The results suggest that changes in GABA receptor-mediated neurotransmission, within the NTS, are involved in the increase in resting ventilation that occurs following CH.

control of breathing; -aminobutyric acid; plethysmography