Effects of chronic administration of phenobarbital in low doses on control of breathing in the cat.

The ventilatory response to CO hypoxia (FICO = 0.0025), hypercapnia, and hypoxia was studied in a group of intact, conscious cats before and during chronic administration of phenobarbital (60 mg/day). It was found that the ventilatory response to hypercapnia or hypoxia was not significantly modified during phenobarbital administration. However, the ventilatory response to CO hypoxia was markedly blunted with phenobarbital: the initial ventilatory inhibition was still observed but the subsequent hyperventilation was delayed. Furthermore, the tachypnea was less intense and the decrease in tidal volume was smaller during CO hypoxia. In addition, the behavioral reactions which usually accompanied the tachypnea were attenuated and unconsciousness was often noted. These results indicate that the modifications caused by phenobarbital do not result from a general inhibition of the respiratory control network but rather from a selective inhibition of the structures rostral to the brain stem. As a consequence, the behavioral reactions and resulting respiratory activation were attenuated. Since the hypoxic tachypnea and behavioral reactions are observed only during central hypoxemia, it is concluded that arterial chemoreceptor afferents normally inhibit the supra-pontine structures which are otherwise stimulated by central hypoxemia.