Fentanyl produces cholinergically-mediated analeptic and EEG arousal effects in rats

Fentanyl (20 micrograms/kg i.p.), administered to naltrexone-pretreated, pentobarbital-anesthetized rats, produced a shortening of the duration of narcosis. This analeptic effect was blocked by atropine, but not by methylatropine, indicating that a central cholinergic mechanism was involved. Fentanyl also increased sodium-dependent high affinity uptake of choline activity in the hippocampus and cortex that had been depressed by the barbiturate. Injection of 0.8 ng of fentanyl into the pontis oralis in the pontine reticular formation also produced analepsis in naltrexone-pretreated, pentobarbitalized rats. Hippocampal EEG recordings also showed the appearance of cholinergically-mediated theta activity, which was indicative of arousal activity in the hippocampus. These results suggest that fentanyl, in addition to possessing potent opiate activity, also activates a nonopioid-mediated central cholinergic arousal system.