The role of inhibitory amino acids in control of respiratory motor output in an arterially perfused rat.

The respiratory effects of drugs affecting GABAergic and glycinergic transmission were examined in order to assess the role of synaptic inhibition in breathing rhythmogenesis. Experiments were performed in the arterially perfused in situ brainstem-spinal cord preparation from adult rats (Hayashi et al., 1991, J. Neurosci. Meth. 36:63-70). Administration to the perfusate of agonists of GABAA, GABAB, and glycine receptors reduced both the frequency and amplitude of the activity recorded from the phrenic and hypoglossal nerves. Similar effects were observed following the infusion of aminooxyacetic acid (a blocker of GABA-transaminase). Picrotoxin (0.1-2 microM), bicuculline (0.05-0.2 microM), strychnine (0.1-1 microM) and phaclofen (0.1-0.2 mM) usually increased the frequency and amplitude of inspiratory bursts. Perfusion with low Cl- (8 mM) solution elicited tonic discharge followed by reversible arrest of the respiratory activity. It is concluded that synaptic inhibition is involved in the respiratory rhythm generation process in the mature mammalian brain. As data from the literature indicate that interference with central inhibitory processes does not largely affect the rhythm generation process in newborn rats, a possibility is discussed that the brainstem respiratory generator undergoes a developmental change from a 'pacemaker' driven circuit at the neonatal stage to a network requiring post-synaptic inhibition in the mature brain.