BackgroundThe activity of canine expiratory neurons is primarily dependent onN‐methyl‐D‐aspartic acid (NMDA)‐receptor mediated excitatory chemodrive inputs and a powerful inhibitory gain modulatory mechanism mediated via &ggr;‐aminobutyric acidA(GABAA) receptors. We examined whether the depressant effect of halothane on expiratory neuronal activity is primarily caused by a reduction in glutamatergic excitation or a potentiation of the inhibitory mechanism.MethodsExperiments were performed in halothane‐anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of a halothane dose increase from one minimum alveolar concentration (MAC) to 2 MAC on extracellularly recorded expiratory neuronal activity was studied before and during complete GABAAreceptor blockade by localized picoejection of bicuculline close to the neuron. Complete blockade of the inhibitory mechanism allowed differentiation between the effects of halothane on overall NMDA‐mediated excitation and on GABAA‐mediated inhibition.ResultsThe spontaneous activity of 12 expiratory neurons was significantly depressed (18.1%) by the 1‐MAC halothane dose increase. Overall glutamatergic excitation was depressed 38.3 ± 12.3% (mean ± SD) by the 1‐MAC halothane increase. The prevailing GABAAergic attenuation of neuronal output decreased significantly from 49.5 ± 10 to 32.0 ± 10.4%. Thus overall inhibition was reduced by halothane by 33.5 ± 17.2%.ConclusionsThese results suggest that the depressive effect of a 1‐MAC halothane dose increase on expiratory neuronal activity in ourin vivopreparation with an intact neural network was mainly caused by a reduction of synaptic excitatory mechanisms and not an enhancement of synaptic inhibitory mechanisms.