Fentanyl inhibits GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

• Published in: Brain research 2004-05, Vol.1007 (1), p.109-115
• Main Authors: Griffioen, Kathleen J.S., Venkatesan, Priya, Huang, Zheng-Gui, Wang, Xin, Bouairi, Evguenia, Evans, Cory, Gold, Allison, Mendelowitz, David
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Analgesics; Anesthetics, Local - pharmacology; Animals; Animals, Newborn; Biological and medical sciences; Drug Interactions; Electrophysiology; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fentanyl; Fentanyl - pharmacology; gamma-Aminobutyric Acid - metabolism; Glycine Agents - pharmacology; Heart - drug effects; In Vitro Techniques; Medical sciences; Medulla Oblongata - cytology; Membrane Potentials - drug effects; Narcotics - pharmacology; Neural Inhibition - drug effects; Neurons - drug effects; Neuropharmacology; Nucleus ambiguus; Opioid; Patch-Clamp Techniques - methods; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Strychnine - pharmacology; Synaptic Transmission - drug effects; Tetrodotoxin - pharmacology; Vagus Nerve - drug effects; Valine - analogs & derivatives; Valine - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.02.010

Fentanyl citrate is a synthetic opiate analgesic often used clinically for neonatal anesthesia. Although fentanyl significantly depresses heart rate, the mechanism of inducing bradycardia remains unclear. One possible site of action is the cardioinhibitory parasympathetic vagal neurons in the nucleus ambiguus (NA), from which originates control of heart rate and cardiac function. Inhibitory synaptic activity to cardiac vagal neurons is a major determinant of their activity. Therefore, the effect of fentanyl on GABAergic neurotransmission to parasympathetic cardiac vagal neurons was studied using whole-cell patch clamp electrophysiology. Application of fentanyl induced a reduction in both the frequency and amplitude of GABAergic IPSCs in cardiac vagal neurons. This inhibition was mediated at both pre- and postsynaptic sites as evidenced by a dual decrease in the frequency and amplitude of spontaneous miniature IPSCs. Application of the selective μ-antagonist CTOP abolished the fentanyl-mediated inhibition of GABAergic IPSCs. These results demonstrate that fentanyl acts on μ-opioid receptors on cardiac vagal neurons and neurons preceding them to reduce GABAergic neurotransmission and increase parasympathetic activity. The inhibition of GABAergic effects may be one mechanism by which fentanyl induces bradycardia.