Anesthesia describes a complex state composed of immobility,
amnesia,
hypnosis (sleep or
loss of consciousness),
analgesia, and muscle relaxation. Bottom-up approaches explain
anesthesia by an interaction of the
anesthetic with receptor
proteins in the brain, whereas top-down 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 years of research have now yielded a complex picture of the effects of
general anesthetics on brain
neurotransmitter basal activity and response dynamics. It is suggested that analyzing the effects on
neurotransmitter activity is the logical next step after
protein interactions in a bottom-up analysis of
anesthetic action in the brain on the way to a unifying view of
anesthesia.