Development of acute tolerance to the cardiorespiratory effects of alfentanil after subsequent bolus injection in conscious rats

The cardiovascular and respiratory effects of alfentanil in conscious freely moving rats, were evaluated after initial and subsequent injections. Doses of alfentanil (50, 130, 260, and 500 ug/kg) were given to naive rats (n = 4-5) and 1 hour later this dose was repeated. The resultant cardiovascular and respiratory effects were compared. At all doses there was a significant (p less than 0.05) depression of mean arterial pressure and heart rate after the initial dose of alfentanil. At doses of 50, 130, and 260 ug/kg, the second administration elicited significantly less depression of cardiovascular parameters than the initial dose. Maximum changes in respiratory parameters (PaCO2 and PaO2) were also significantly less after the second administration of alfentanil. This difference, in maximum respiratory depression, was not seen at the highest doses (500 ug/kg). These results indicate that tolerance, to the cardiorespiratory side effects seen after alfentanil, can occur in as little as 1 hour after subsequent bolus injections.