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Bottom\u2010up approaches explain anesthesia by an interaction of the anesthetic with receptor proteins in the brain, whereas top\u2010down approaches consider predominantly cortical and thalamic network activity and connectivity. Both approaches have a number of explanatory gaps and as yet no unifying view has emerged. In addition to a direct interaction with primary target receptor proteins, general anesthetics have massive effects on neurotransmitter activity in the brain. They can change basal transmitter levels by interacting with neuronal activity, transmitter synthesis, release, reuptake and metabolism. By that way, they can affect a great number of neurotransmitter systems and receptors. Here, we review how different general anesthetics affect extracellular activity of neurotransmitters in the brain during induction, maintenance, and emergence from anesthesia and which functional consequences this may have. Commonalities and differences between different groups of anesthetics in their action on neurotransmitter activity are discussed. We also review how general anesthetics affect the response dynamics of the neurotransmitter systems after sensory stimulation. More than 30\u2003years of research have now yielded a complex picture of the effects of general anesthetics on brain neurotransmitter basal activity and response dynamics. 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