Effects of naloxone on oxygen consumption and ventilation in awake golden Syrian hamsters

Endogenous opioids are known to inhibit chemoreception and ventilatory control. The opioid antagonist naloxone stimulates ventilation by removing this inhibition. To study whether the effects of opiate receptor antagonism are mediated by a central or a peripheral mechanism, we administered equal doses of naloxone hydrochloride (NHCl, an agent that crosses the blood-brain barrier) and naloxone methiodide (NM, an agent that does not cross the blood-brain barrier) to awake golden Syrian hamsters. Both naloxone preparations significantly increased the oxygen consumption (46% for NHCl and 90% for NM) in these animals relative to saline. Naloxone hydrochloride, but not NM, stimulated ventilation (30%) and tidal volume (34%) when the animal was subjected to a hypercapnic challenge, predominantly sensed in the brain. In contrast, both naloxones stimulated ventilation by 52% compared to saline treatment when the hamsters were exposed to a hypoxic challenge, predominantly sensed peripherally. These results suggest that endogenous opioids modulate both central and peripheral chemoreception in the hamster.