NDLI: Benzodiazepine site agonists differentially alter acetylcholine release in rat amygdala.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hambrecht-Wiedbusch, Viviane S. Mitchell, Melinda F. Firn, Kelsie A. Baghdoyan, Helen A. Lydic, Ralph
Description	Author Affiliation: Hambrecht-Wiedbusch VS ( From the Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.)
Abstract	BACKGROUND: Agonist binding at the benzodiazepine site of Î³-aminobutric acid type A receptors diminishes anxiety and insomnia by actions in the amygdala. The neurochemical effects of benzodiazepine site agonists remain incompletely understood. Cholinergic neurotransmission modulates amygdala function, and this study tested the hypothesis that benzodiazepine site agonists alter acetylcholine (ACh) release in the amygdala. METHODS: Microdialysis and high-performance liquid chromatography quantified ACh release in the amygdala of Sprague-Dawley rats (n = 33). ACh was measured before and after IV administration (3 mg/kg) of midazolam or eszopiclone, with and without anesthesia. ACh in isoflurane-anesthetized rats during dialysis with Ringer's solution (control) was compared with ACh release during dialysis with Ringer's solution containing (100 µM) midazolam, diazepam, eszopiclone, or zolpidem. RESULTS: In unanesthetized rats, ACh in the amygdala was decreased by IV midazolam (-51.1%; P = 0.0029; 95% confidence interval [CI], -73.0% to -29.2%) and eszopiclone (-39.6%; P = 0.0222; 95% CI, -69.8% to -9.3%). In anesthetized rats, ACh in the amygdala was decreased by IV administration of midazolam (-46.2%; P = 0.0041; 95% CI, -67.9% to -24.5%) and eszopiclone (-34.0%; P = 0.0009; 95% CI, -44.7% to -23.3%), and increased by amygdala delivery of diazepam (43.2%; P = 0.0434; 95% CI, 2.1% to 84.3%) and eszopiclone (222.2%; P = 0.0159; 95% CI, 68.5% to 375.8%). CONCLUSIONS: ACh release in the amygdala was decreased by IV delivery of midazolam and eszopiclone. Dialysis delivery directly into the amygdala caused either increased (eszopiclone and diazepam) or likely no significant change (midazolam and zolpidem) in ACh release. These contrasting effects of delivery route on ACh release support the interpretation that systemically administered midazolam and eszopiclone decrease ACh release in the amygdala by acting on neuronal systems outside the amygdala.
File Format	HTM / HTML
ISSN	00032999
e-ISSN	15267598
DOI	10.1213/ANE.0000000000000201
Journal	Anesthesia & Analgesia
Issue Number	6
Volume Number	118
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2014-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Anesthesiology Acetylcholine Metabolism Amygdala Gaba Agonists Pharmacology Receptors, Gaba-a Drug Effects Anesthesia, Inhalation Anesthetics, Inhalation Animals Azabicyclo Compounds Chromatography, High Pressure Liquid Diazepam Eszopiclone Administration & Dosage Injections, Intravenous Isoflurane Microdialysis Midazolam Piperazines Pyridines Rats, Sprague-dawley Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Anesthesiology and Pain Medicine

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Benzodiazepine Site Agonists Differentially Alter Acetylcholine Release in Rat Amygdala

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Benzodiazepine site agonists differentially alter acetylcholine release in rat amygdala.

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Benzodiazepine Site Agonists Differentially Alter Acetylcholine Release in Rat Amygdala

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Benzodiazepine site agonists differentially alter acetylcholine release in rat amygdala.