Isoflurane causes concentration-dependent inhibition of medullary raphé 5-HT neurons in situ.

Abstract

Anesthetics have a profound influence on a myriad of autonomic processes. Mechanisms of general anesthesia, and how these mechanisms give rise to the multifaceted state of anesthesia, are largely unknown. The ascending and descending serotonin (5-HT) networks are key modulators of autonomic pathways, and are critically involved in homeostatic reflexes across the motor, somatosensory, limbic and autonomic systems. These 5-HT networks are thought to contribute to anesthetic effects, but how anesthetics affect 5-HT neuron function remains a pertinent question. We hypothesized that the volatile anesthetic isoflurane inhibits action potential discharge of medullary raphé 5-HT neurons. We conducted extracellular recordings on individual neurons in the medullary raphé region of the unanesthetized in situ perfused brainstem preparation to determine how exposure to isoflurane affects 5-HT neurons. We examined changes in 5-HT neuron baseline firing in response to treatment with either 1, 1.5, or 2% isoflurane. We measured isoflurane concentrations by gas chromatography-mass spectrometry (GC-MS) analysis. Exposure to isoflurane inhibited action potential discharge in raphé 5-HT neurons. We document a concentration-dependent inhibition over a range of concentrations approximating isoflurane MAC (minimum alveolar concentration required for surgical anesthesia). Delivered concentrations of isoflurane were confirmed using GC-MS analysis. These findings illustrate that halogenated anesthetics greatly affect 5-HT neuron firing and suggest 5-HT neuron contributions to mechanisms of general anesthesia.