Influences of endogenous dopamine on carotid body discharge and ventilation

Ventilatory and carotid body responses to hypoxia have been related to the endogenous release of dopamine by use of the antagonist drug haloperidol. The published studies have produced conflicting data for ventilation. However, antagonist drugs can act at multiple anatomical sites, on multiple pharmacological receptors, often at different dosages, and have nonspecific actions at high dosage. For these reasons, we have undertaken a systematic study of haloperidol dose-response curves with particular emphasis on the lowest possible concentrations of drug. In five cats anesthetized with pentobarbital sodium (30-35 mg/kg), single- or few-fiber afferent recordings of the carotid body showed that haloperidol increased the discharge during both basal and asphyxic conditions, the increments being proportional to haloperidol dosage (0.1-1,000 micrograms/kg). Increments of ventilation were also produced, these increments increasing only over the lower range of dosage; at the highest haloperidol dosage, the dose response showed a tendency to plateau or inflect downward, suggesting the appearance of an opposing inhibitory mechanism.