It is possible to study the effects of anesthesia at specific sites in the brain by placing a cannula directly into the tissue of interest, injecting the drug of interest, and measuring neurotransmitter release as well as systemic response. The amygdaloid nuclear complex, located bilaterally in the temporal lobes, modulates both sleep and anxiety. Dr. Ralph Lydic, Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, and coauthors sought to determine the effect of GABAergic sedative/hypnotic drugs on the release of acetylcholine (ACh) in the amygdala. The results of their study are published in this month’s edition of Anesthesia & Analgesia in the article titled “Benzodiazepine Site Agonists Differentially Alter Acetylcholine Release in Rat Amygdala.”
Midazolam and eszopiclone, a benzodiazepine agonist, were administered intravenously to alert and isoflurane-anesthetized animals. Under both conditions, both agents caused a 40-50% decrease in ACh release in the amygdala as measured using a microperfusion technique. This makes sense since other studies have shown that eszopiclone also decreases ACh release in sleep-promoting regions of the pontine reticular formation. Diazepam, zolpidem, midazolam and eszopiclone were subsequently administered via dialysis directly into the amygdala in anesthetized animals. Direct administration of diazepam and eszopiclone significantly increased the release of ACh by 43-222%.
This study has some interesting implications for understanding anesthetic actions. Amygdala activation causes the release of an increase in neurotransmitters, yet benzodiazepine agonists enhance GABAergic inhibition, thus resulting in diminished excitability within the amygdala. These research results emphasize the concept that multiple experimental approaches are needed when studying the effects of a drug and that microdialysis of a drug in a particular site does not necessarily mean that site is the same brain site in which systemically administered drugs alter neurotransmitter levels. Returning to the specifics of this study, the GABAergic agonists midazolam and eszopiclone affect ACh release in the amygdala remotely by acting on neuronal systems outside of the amygdala.