Are cholinergic pathways involved in the anesthetic response to alpha2 agonists

1. We investigated whether change in neuronal activity in cholinergic pathways mediates the anesthetic effect of the alpha2 agonist, dexmedetomidine, by determining whether physostigmine, a cholinesterase inhibitor, could antagonize the hypnotic response to dexmedetomidine in the rat and whether dexmedetomidine decreases the release of acetylcholine (ACh) in the thalamus in vivo. 2. Physostigmine did not significantly change the duration of the hypnotic response to dexmedetomidine. There was no significant change in thalamic ACh release after administration of dexmedetomidine. Therefore, alpha2-adrenergic agonists produce their anesthetic effect through mechanisms which do not involve alteration of the activity of the brainstem cholinergic nuclei.