Alfentanil-induced hypermetabolism, seizure, and histopathology in rat brain

We evaluated the effect of alfentanil on hippocampal glucose utilization and histopathology associated with alfentanil-induced seizures. Three separate experiments were performed. First, anesthetized, paralyzed Long-Evans rats (n = 15; 5 rats per group) were mechanically ventilated and randomly assigned to three groups: (a) control, 70% N2O and 30% O2 continued for 1 h; (b) low-dose alfentanil (150 micrograms/kg i.v. bolus), followed by infusion at 15 micrograms.kg-1 x min-1 for 1 h without N2O; or (c) high-dose alfentanil (1000 micrograms/kg i.v. bolus), followed by infusion at 100 micrograms.kg-1 x min-1 for 1 h without N2O. After 1 h, [6-14C]glucose was injected intravenously for autoradiography. With high-dose alfentanil, there was increased glucose utilization in the ventral hippocampus and the lateral septal nucleus. In the second experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 12; 4 rats per group) were mechanically ventilated, underwent insertion of hippocampal depth electrodes, and were randomly assigned to three groups: (a) control, 70% N2O and 30% O2; (b) low-dose alfentanil (150 micrograms/kg i.v. bolus), with 70% N2O and 30% O2; or (c) high-dose alfentanil (1000 micrograms/kg i.v. bolus), with 70% N2O and 30% O2. An epileptiform pattern was observed on hippocampal and subdermal electroencephalographic recordings in both alfentanil groups. In the third experiment, anesthetized, paralyzed Sprague-Dawley rats (n = 20) were mechanically ventilated and assigned to two groups: (a) control, 70% N2O and 30% O2 (n = 5) or 100% O2 (n = 5) continued for 1 h; or (b) alfentanil (2000 micrograms/kg i.v. bolus), followed by infusion at 33.3 micrograms.kg-1 x min-1 for 1 h with 100% O2. After tracheal extubation, the rats recovered overnight. Light-microscopic evaluation revealed hippocampal or amygdaloid damage in 6 of the 10 alfentanil-treated rats. High doses of alfentanil administered to rats can produce limbic system seizure activity with hypermetabolism associated with neuropathologic lesions.